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  • 1. Andersson, Åsa
    et al.
    Isaksson, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wefer, Judit
    Norling, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Flores-Morales, Amilcar
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Harris, Robert A.
    Lobell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Impaired autoimmune T helper 17 cell responses following DNA vaccination against rat experimental autoimmune encephalomyelitis2008Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 3, nr 11, s. e3682-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)(91-108) (pMOG) suppresses MOG(91-108)-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive effect of pMOG is dependent on inclusion of CpG DNA in the plasmid backbone and is associated with early induction of Interferon (IFN)-beta. PRINCIPAL FINDINGS: In this study we examined the mechanisms underlying pMOG-induced protection. We found that in the DNA vaccinated cohort proinflammatory Interleukin (IL)-17 and IL-21 responses were dramatically reduced compared to in the control group, but that the expression of Foxp3 and Tumor Growth Factor (TGF)-beta1, which are associated with regulatory T cells, was not enhanced. Moreover, genes associated with Type I IFNs were upregulated. To delineate the role of IFN-beta in the protective mechanism we employed short interfering RNA (siRNA) to IFN-beta in the DNA vaccine. SiRNA to IFN-beta completely abrogated the protective effects of the vaccine, demonstrating that a local early elaboration of IFN-beta is important for EAE protection. IL-17 responses comparable to those in control rats developed in rats injected with the IFN-beta-silencing DNA vaccine. CONCLUSIONS: We herein demonstrate that DNA vaccination protects from proinflammatory Th17 cell responses during induction of EAE. The mechanism involves IFN-beta as IL-17 responses are rescued by silencing of IFN-beta during DNA vaccination.

  • 2.
    Bensing, Sophie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Crock, P.
    Sanjeevi, C.
    Ericson, K.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Brismar, K.
    Hulting, A-L.
    No evidence for autoimmunity as a major cause of the empty sella syndrome2004Ingår i: Experimental and clinical endocrinology & diabetes, ISSN 0947-7349, E-ISSN 1439-3646, Vol. 112, nr 5, s. 231-235Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    OBJECTIVE: The cause of empty sella syndrome (ESS) remains largely unknown. We measured eleven organ-specific autoantibodies in serum in order to evaluate possible autoimmune components in ESS. PATIENTS: Thirty patients with ESS and 50 healthy blood donors participated in the study. MEASUREMENTS: Detection of pituitary autoantibodies was performed by immunoblotting with human pituitary cytosol as antigen. Thyroid peroxidase (TPO) and TSH receptor (TRAK) autoantibodies were analysed by radioimmunoassay. The remaining eight autoantibodies were detected by in vitro transcription and translation of the autoantigens and immunoprecipitation. RESULTS: The majority of the ESS patients (18/30) exhibited no immunoreactivity at all. None of the remaining 12 ESS patients reacted against more than one autoantigen. No immunoreactivity was found more frequently among ESS patients than healthy blood donors. Pituitary autoantibodies were not correlated to the ESS patients' pituitary function or sellar size, although the results indicated a tendency of increased autoimmunity in patients with hypopituitarism and normal sella size respectively. CONCLUSION: Detection of autoantibodies is a valuable tool in the diagnostic work-up of autoimmune diseases. By analysing a large number of organ-specific autoantibodies we found no evidence of ESS being associated with any specific autoimmune disease. The pathogenesis of ESS is believed to be heterogeneous and our findings suggest autoimmune components to be of minor importance. In some selective cases, ESS in combination with hypopituitarism may be the result of an autoimmune disease in the pituitary gland but this needs further investigation.

  • 3.
    Borssen, Åsa D.
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Palmqvist, Richard
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden..
    Kechagias, Stergios
    Linkoping Univ, Dept Med & Hlth Sci, Dept Gastroenterol & Hepatol, Linkoping, Sweden..
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden..
    Bergquist, Annika
    Karolinska Univ, Huddinge Hosp, Dept Med, Sect Hepatol & Gastroenterol,Karolinska Inst, Stockholm, Sweden..
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Weiland, Ola
    Karolinska Univ, Huddinge Hosp, Div Infect Dis, Dept Med,Karolinska Inst, Stockholm, Sweden..
    Verbaan, Hans
    Lund Univ, Gastroenterol Div, Dept Clin Sci, Univ Hosp Skane, Lund, Sweden..
    Nyhlin, Nils
    Orebro Univ, Dept Gastroenterol, Fac Med & Hlth, Orebro, Sweden..
    Nilsson, Emma
    Lund Univ, Gastroenterol Div, Dept Clin Sci, Univ Hosp Skane, Lund, Sweden..
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis A cohort study2017Ingår i: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, nr 34, artikel-id e7708Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis. A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared. Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy. Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

  • 4.
    Borssen, Åsa Danielsson
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Bergquist, Annika
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Sect Hepatol & Gastroenterol, Dept Med, Stockholm, Sweden..
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Weiland, Ola
    Karolinska Univ Hosp Huddinge, Karolinska Inst, Div Infect Dis, Dept Med, Stockholm, Sweden..
    Kechagias, Stergios
    Univ Hosp, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Nyhlin, Nils
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden..
    Verbaan, Hans
    Lund Univ, Univ Hosp Skane, Div Gastroenterol, Dept Clin Sci, Malmo, Sweden..
    Nilsson, Emma
    Lund Univ, Univ Hosp Skane, Div Gastroenterol, Dept Clin Sci, Lund, Sweden..
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis2017Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 9, s. 1022-1028Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.Material and methods: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Vasterbotten in Northern Sweden.Results: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p<.001) and died younger than women (p=.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.Conclusions: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

  • 5.
    Efe, Cumali
    et al.
    Gazi Yasargil Educ & Res Hosp, Dept Gastroenterol, Diyarbakir, Turkey.
    Tascilar, Koray
    Istanbul Okmeydani Educ & Res Hosp, Dept Rheumatol, Istanbul, Turkey.
    Henriksson, Ida
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, Orebro, Sweden.
    Lytvyak, Ellina
    Univ Alberta, Div Gastroenterol, Edmonton, AB, Canada;Univ Alberta, Liver Unit, Edmonton, AB, Canada.
    Alalkim, Fatema
    Univ British Columbia, Div Gastroenterol, Vancouver, BC, Canada;Vancouver Gen Hosp, Vancouver, BC, Canada.
    Trivedi, Hirsh
    Harvard Med Sch, Beth Israel Med Ctr, Div GI & Hepatol, Boston, MA 02115 USA.
    Eren, Fatih
    Uludag Univ, Med Fac, Dept Gastroenterol, Bursa, Turkey.
    Eliasson, Johanna
    Univ Copenhagen, Rigshosp, Dept Hepatol, Copenhagen, Denmark.
    Beretta-Piccoli, Benedetta Terziroli
    Epatoctr Ticino, Dept Internal Med, Lugano, Switzerland.
    Fischer, Janett
    Univ Clin Leipzig, Sect Hepatol, Clin Gastroenterol, Leipzig, Germany.
    Caliskan, Ali Riza
    Inonu Univ, Sch Med, Dept Gastroenterol, Malatya, Turkey.
    Chayanupatkul, Maneerat
    Mt Sinai Med Ctr, Div Liver Dis, New York, NY 10029 USA;Chulalongkorn Univ, Fac Med, Bangkok, Thailand.
    Coppo, Claudia
    Univ Bologna, Ctr Study & Treatment Autoimmune Dis Liver & Bili, Bologna, Italy.
    Ytting, Henriette
    Univ Copenhagen, Rigshosp, Dept Hepatol, Copenhagen, Denmark.
    Purnak, Tugrul
    Hacettepe Univ, Dept Gastroenterol, Ankara, Turkey.
    Muratori, Luigi
    Univ Bologna, Ctr Study & Treatment Autoimmune Dis Liver & Bili, Bologna, Italy.
    Werner, Mårten
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Muratori, Paolo
    Univ Bologna, Ctr Study & Treatment Autoimmune Dis Liver & Bili, Bologna, Italy.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Önnerhag, Kristina
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden.
    Günsar, Fulya
    Ege Univ, Dept Gastroenterol, Izmir, Turkey.
    Nilsson, Emma
    Lund Univ, Univ Hosp Skane, Dept Clin Sci, Gastroenterol Div, Lund, Sweden.
    Heurgue-Berlot, Alexandra
    CHU Reims, Dept Hepatogastroenterol, Reims, France.
    Güzelbulut, Fatih
    Haydarpasa Numune Educ & Res Hosp, Dept Gastroenterol, Istanbul, Turkey.
    Demir, Nurhan
    Gazi Yasargil Educ & Res Hosp, Dept Gastroenterol, Diyarbakir, Turkey.
    Gönen, Can
    Haydarpasa Numune Educ & Res Hosp, Dept Gastroenterol, Istanbul, Turkey.
    Semela, David
    Kantonsspital St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland.
    Aladag, Murat
    Inonu Univ, Sch Med, Dept Gastroenterol, Malatya, Turkey.
    Kiyici, Murat
    Uludag Univ, Med Fac, Dept Gastroenterol, Bursa, Turkey.
    Schiano, Thomas
    Mt Sinai Med Ctr, Div Liver Dis, New York, NY 10029 USA.
    Montano-Loza, Aldo
    Univ Alberta, Div Gastroenterol, Edmonton, AB, Canada;Univ Alberta, Liver Unit, Edmonton, AB, Canada.
    Berg, Thomas
    Univ Clin Leipzig, Sect Hepatol, Clin Gastroenterol, Leipzig, Germany.
    Ozaslan, Ersan
    Numune Res & Educ Hosp, Dept Gastroenterol, Ankara, Turkey.
    Yoshida, Eric
    Univ British Columbia, Div Gastroenterol, Vancouver, BC, Canada;Vancouver Gen Hosp, Vancouver, BC, Canada.
    Bonder, Alan
    Harvard Med Sch, Beth Israel Med Ctr, Div GI & Hepatol, Boston, MA 02115 USA.
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.
    Wahlin, Staffan
    Karolinska Inst, Ctr Digest Dis, Hepatol Div, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis2019Ingår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 114, nr 7, s. 1101-1108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts.

    METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points.

    RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%).

    DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

  • 6.
    Englund, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Jacobson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Efflux transporters in ulcerative colitis: decreased expression of BCRP (ABCG2) and Pgp (ABCB1)2007Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, nr 3, s. 291-297Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Efflux transport proteins are important components of the intestinal barrier against bacterial toxins, carcinogens, and drugs. This investigation was conducted to determine the expression of Breast Cancer Resistance Protein (BCRP/ABCG2), P-glycoprotein (Pgp/MDR1/ABCB1), and Multidrug Resistance Protein 2 (MRP2/ABCC2) in the gut mucosa of patients with ulcerative colitis (UC). Methods: Patients were thoroughly diagnosed according to well-established clinical, endoscopic, and histologic criteria to be included in the group of patients with active UC (n = 16) or UC in remission (n = 17). Colonic and rectal mucosa from patients with UC were compared with tissues from control subjects (n = 15). The mRNA expression (TaqMan) of the efflux transporters and the proinflammatory cytokines interleukin (IL)-1β and IL-6 was determined. Western blot was used in the analysis of protein expression and the tissue localization of BCRP was determined with confocal microscopy. Results: BCRP and Pgp expression was strongly reduced in individuals with active inflammation compared with controls and was negatively correlated with the levels of IL-6 mRNA. The BCRP staining of colonic epithelium seen in healthy mucosa was diminished in inflamed tissues, with concurrent disruption of epithelial F-actin structure. Conclusions: Two of the efflux transporters of importance for the barrier function of the gut mucosa, Pgp and BCRP, are expressed at strongly reduced levels during active inflammation in patients with UC. Investigations are warranted to determine whether the low levels of efflux transporters during active UC contribute to altered transport and tissue exposure of carcinogens, bacterial toxins, and drugs.

  • 7.
    Englund, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karlbom, Urban
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lazorova, Lucia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Gråsjö, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Artursson, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Regional levels of drug transporters along the human intestinal tract: Co-expression of ABC and SLC transporters and comparison with Caco-2 cells2006Ingår i: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 29, nr 3-4, s. 269-277Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A vast number of drugs are subjected to active or facilitated transport and multiple transport mechanism may contribute to the net flux during drug absorption. The main objective of this study was to quantify the regional mRNA expression and determine the co-expression of drug transporters from the ABC (Pgp, BCRP, MRP2, MRP3) and SLC (PEPT1, MCT1, OATPB, OCTN2, OCT1) families along the human intestine (duodenum, jejunum, ileum, and colon). A second objective was to compare the transporter expression between the different intestinal regions and Caco-2 cells. Eight out of nine of the investigated transporters exhibited significant regional differences in expression. OATPB was the only transporter that did not show a region-dependency in the expression along the human intestinal canal. The expression of Pgp, BCRP, OCTN2 and MCT1 differed along the small intestine, but the expression differences were greater than five-fold only for Pgp. The rank order of transcript prevalence was identical in the ileum and the jejunum. Between the ileum and colon, seven transcripts were differentially expressed, and MCT1, OCTN2 and MRP3 were expressed at higher levels in the colon than in the small intestine. The expression of transporters in Caco-2 was closest to the expression pattern in the small intestine, although the expression of OATPB, BCRP and MRP2 differed more than five-fold between the Caco-2 cells and ileum. In conclusion, this study provides quantitative data on the expression of transporters from the ABC and SLC families along the human intestine, which can be useful in the interpretation of clinical studies where more than one intestinal transporter contribute to the net transport and in the computer modelling of drug absorption.

  • 8.
    Gustafsson, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Alimohammadi, Mohammad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ekwall, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gebre-Medhin, Gennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Halldin-Stenlid, Maria
    Hedstrand, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Landgren, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nilsson, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sköldberg, Filip
    Winqvist, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    APSI - svår autoimmun sjukdom med endokrina och icke-endokrina symtom2004Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, nr 24, s. 2096-2103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune polyglandular syndrome type I (APS I) is an autosomal recessive disorder characterized by a combination of autoimmune manifestations affecting endocrine and non-endocrine organs. APS I usually presents in childhood. The three most common manifestations are chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. At least two of these must be present to fulfill the diagnostic criteria of this syndrome. The spectrum of other associated diseases includes gonadal insufficiency, alopecia, vitiligo and chronic active hepatitis. APS I is caused by a mutation in the AIRE-gene (autoimmune regulator) located on chromosome 21. Analysis of specific autoantibodies against intracellular enzymes, particularly enzymes in the synthesis of steroids and neurotransmittors, can be used in the diagnosis of APS I and to predict different manifestations of the disease.

  • 9.
    Hagström, Hannes
    et al.
    Karolinska Univ Hospital, Dept Med, Ctr Digest Dis, Hepatol Unit, Huddinge, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Nasr, Patrik
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Ekstedt, Mattias
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Kechagias, Stergios
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Onnerhag, Kristina
    Lund Univ, Skane Univ Hosp, Dept Gastroenterol & Hepatol, Lund, Sweden..
    Nilsson, Emma
    Lund Univ, Skane Univ Hosp, Dept Gastroenterol & Hepatol, Lund, Sweden..
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sheikhi, Reza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Stal, Per
    Karolinska Univ Hospital, Dept Med, Ctr Digest Dis, Hepatol Unit, Huddinge, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Hultcrantz, Rolf W.
    Karolinska Univ Hospital, Dept Med, Ctr Digest Dis, Hepatol Unit, Huddinge, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease2016Ingår i: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 63, nr 1 SUPP, s. 18A-19AArtikel i tidskrift (Refereegranskat)
  • 10.
    Hagström, Hannes
    et al.
    Karolinska Univ Hosp, Div Hepatol, Ctr Digest Dis, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Nasr, Patrik
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Ekstedt, Mattias
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Kechagias, Stergios
    Linkoping Univ, Dept Gastroenterol & Hepatol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Önnerhag, Kristina
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden..
    Nilsson, Emma
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden..
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sheikhi, Reza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Marschall, Hanns-Ulrich
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Hultcrantz, Rolf
    Karolinska Univ Hosp, Div Hepatol, Ctr Digest Dis, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Stål, Per
    Karolinska Univ Hosp, Div Hepatol, Ctr Digest Dis, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease2017Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 2, s. 159-165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD. Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled. Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p = .017). The lowest risk for fibrosis was found with the lowest odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p = .006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth >= 0.3 mu mol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p = .047). Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.

  • 11. Halonen, M
    et al.
    Eskelin, P
    Myhre, AG
    Perheentupa, J
    Husebye, ES
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Peltonen, L
    Ulmanen, I
    Partanen, J
    AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype2002Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 87, nr 6, s. 2568-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, OMIM 240300) is a rare autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21q22.3. This monogenic disease provides an interesting model for studies of other common and more complex autoimmune diseases. The most common components of APECED are chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison’s disease, but several other endocrine deficiencies and ectodermal dystrophies also occur and the phenotype varies widely. The AIRE genotype also varies; 42 different mutations have been reported so far. To understand the complexity of the phenotype, we studied the AIRE and human leukocyte antigen (HLA) class II genotypes in a series of patients with APECED. The only association between the phenotype and the AIRE genotype was the higher prevalence of candidiasis in the patients with the most common mutation, R257X, than in those with other mutations. Addison’s disease was associated with HLA-DRB1*03 (P = 0.021), alopecia with HLA-DRB1*04- DQB1*0302 (P < 0.001), whereas type 1 diabetes correlated negatively with HLA-DRB1*15-DQB1*0602 (P = 0.036). The same HLA associations have previously been established for non-APECED patients. We conclude that mutation of AIRE per se has little influence on the APECED phenotype, whereas, in contrast to earlier reports, HLA class II is a significant determinant.

  • 12.
    Hjorth, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Sjöberg, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Svanberg, Anncarin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap. Dalarna University, Falun, Sweden.
    Kaminsky, Elenor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälso- och sjukvårdsforskning.
    Langenskiöld, Sophie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Folkhälsovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälsoekonomi.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Nurse-led clinic for patients with liver cirrhosis-effects on health-related quality of life: study protocol of a pragmatic multicentre randomised controlled trial.2018Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, nr 10, artikel-id e023064Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Liver cirrhosis affects health-related quality of life (HRQoL) even in its early stages. Morbidity is especially high when the disease decompensates and self-care actions become essential. Nurse involvement in secondary prevention in other chronic diseases has contributed to better symptom control, less need of inpatient care and improved HRQoL. In order to evaluate the impact of nurse involvement in the follow-up of patients with liver cirrhosis, we decided to compare structured nurse-led clinics, inspired by Dorothea Orem's nursing theory and motivational strategies, with a group of patients receiving standard care. The primary outcome is HRQoL and the secondary outcomes are quality of care, visits to outpatient clinics or hospitals, disease progress and health literacy.

    METHODS AND ANALYSIS: This is a pragmatic, multicentre randomised controlled study conducted at six Swedish hepatology departments. Eligible patients are adults with diagnosed cirrhosis of the liver (n=500). Participants are randomised into either an intervention with nurse-led follow-up group or into a standard of care group. Recruitment started in November 2016 and is expected to proceed until 2020. Primary outcomes are physical and mental HRQoL measured by RAND-36 at enrolment, after 1 and 2 years.

    ETHICS AND DISSEMINATION: The study is ethically approved by the Regional Ethical Review Board in Uppsala. The results shall be disseminated in international conferences and peer-reviewed articles.

    TRIAL REGISTRATION NUMBER: NCT02957253; Pre-results.

  • 13.
    Lampinen, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Fredricsson, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Vessby, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Martinez, Johana Fernandez
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Wanders, Alkwin
    Umeå Univ, Dept Med Biosci, Umeå, Sweden.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Downregulated eosinophil activity in ulcerative colitis with concomitant primary sclerosing cholangitis2018Ingår i: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 104, nr 1, s. 173-183Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Primary sclerosing cholangitis (PSC) is a chronic bile duct inflammation strongly connected to ulcerative colitis (UC). PSC is associated with an increased risk of colon cancer, but the link between the intestinal and the bile duct inflammation is still unknown. Also, the involvement of intestinal immune cells in the pathogenesis of PSC remains to be determined. The eosinophil granulocyte is one of the immune cells implicated in the inflammatory process of ulcerative colitis. This study was performed to determine how the accumulation and activation of intestinal eosinophils may differ between UC with and without concomitant PSC, and how this may be influenced by the cytokine/chemokine profile of the intestinal compartment. Eosinophils from peripheral blood and multiple parts of the colon were analyzed by flow cytometry. The intestinal level of inflammatory mediators was assessed using a multiplex proximity extension assay and a quantitative immunoassay. We found that colonic eosinophils were more abundant in both UC and PSC-UC compared with controls, but that their expression of activation markers was significantly increased in UC only. The colonic level of pro-inflammatory cytokines was increased in active UC but not in PSC-UC. In conclusion, we show for the first time that eosinophil activation phenotype discriminates between UC and PSC-UC, and that this may depend on the local cytokine profile of the colonic mucosa. Lower expression of activation markers on eosinophils in UC with concomitant PSC may depend on the local protein profile of the colonic mucosa.

  • 14.
    Lampinen, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Fredricsson, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Vessby, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Wanders, A.
    Umea Univ, Med Biosci, Umea, Sweden..
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Uppsala Univ, Med Sci, Uppsala, Sweden..
    Expression of the liver homing receptor CXCR3+on colonic CD8+T lymphocytes in patients with primary sclerosing cholangitis provides a possible link between colonic and biliary duct inflammation2016Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, s. S109-S109Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Lampinen, Maria
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Medicin.
    Rönnblom, Anders
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. OTM.
    Amin, Kawa
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. klinisk kemi.
    Kristjansson, Gudjon
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. OTM.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. OTM.
    Sangfelt, Per
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. OTM.
    Säfsten, Bengt
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. OTM.
    Wagner, Michael
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. OTM.
    Wanders, Alkwin
    Institutionen för genetik och patologi. patologi.
    Winqvist, Ola
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Medicin.
    Carlson, Marie
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. OTM.
    Eosinophil granulocytes are activated during the remission phase of ulcerative colitis.2005Ingår i: Gut, ISSN 0017-5749Artikel i tidskrift (Refereegranskat)
  • 16.
    Lampinen, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Vessby, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Fredricsson, Annika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Wanders, Alkwin
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Carlson, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    High serum sCD40 and a distinct colonic T cell profile in ulcerative colitis associated with primary sclerosing cholangitis.2019Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, nr 3, s. 341-350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: There is a strong association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC), but the immunological link between the two diseases is obscure. We compared serum cytokine profiles of patients with PSC-UC and UC, and investigated a number of selected cytokines in colonic biopsy samples. We also assessed the presence and activation of T-cells in peripheral blood and colonic mucosa.

    Methods: Serum samples from 22 patients with PSC-UC, 28 patients with UC and 19 controls were analyzed by a proximity extension assay including 92 inflammatory cytokines. Biopsies from caecum, sigmoid colon and rectum were collected from the same patients. Quantitative analysis for IFN-γ, IL-2, IL-4, IL-5, IL-13, IL-17A/ E/F, IL-21, IL-22, IL-23 and IL-27 was carried out on tissue homogenates. T-cell phenotype was evaluated by flow cytometry.

    Results: By multivariate analysis we identified a cluster of serum cytokines with higher levels in PSC-UC, and sCD40 in particular was strongly associated to this patient group. In contrast, colonic cytokines were only modestly increased in PSC-UC, whereas several Th1, Th2 and Th17-associated cytokines were increased in UC. Patients with PSC-UC had increased colonic levels of CXCR3-positive CD8+ T-cells but fewer CD25-positive CD4+ T-cells. An increased CRTH2/CXCR3-quote indicated a predominance of Th-2 type CD4+ T-cells in UC-patients.

    Conclusions: Our study reveals different cytokine- and T-cell profiles in PSC-UC and UC, with higher systemic levels of cytokines in PSC-UC, and a more pronounced colonic inflammation in UC. Serum sCD40 could potentially be investigated as a marker for PSC in UC.

  • 17.
    Landegren, Nils
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Pourmousa Lindberg, Mina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Skov, Jakob
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Hallgren, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Eriksson, Daniel
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Lisberg Toft-Bertelsen, Trine
    Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark.
    MacAulay, Nanna
    Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark.
    Hagforsen, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Räisänen-Sokolowski, Anne
    Helsinki Univ Hosp, Dept Pathol, Helsinki, Finland.; Univ Helsinki, Helsinki, Finland.
    Saha, Heikki
    Tampere Univ Hosp, Sch Med, Dept Med, Tampere, Finland.
    Nilsson, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Ohlsson, Sophie
    Lund Univ, Dept Nephrol, Lund, Sweden.
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Husebye, Eystein S
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.; Univ Bergen, Dept Clin Sci, Bergen, Norway.; Haukeland Hosp, Dept Med, Bergen, Norway.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Anderson, Mark S
    Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
    Perheentupa, Jaakko
    Univ Helsinki, Hosp Children & Adolescents, Helsinki, Finland.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Fenton, Robert A
    Aarhus Univ, Dept Biomed, Interact Prot Epithelial Transport Ctr, Aarhus, Denmark.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, SE-17176 Stockholm, Sweden.
    Autoantibodies Targeting a Collecting Duct-Specific Water Channel in Tubulointerstitial Nephritis.2016Ingår i: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, nr 10, s. 3220-3228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tubulointerstitial nephritis is a common cause of kidney failure and may have diverse etiologies. This form of nephritis is sometimes associated with autoimmune disease, but the role of autoimmune mechanisms in disease development is not well understood. Here, we present the cases of three patients with autoimmune polyendocrine syndrome type 1 who developed tubulointerstitial nephritis and ESRD in association with autoantibodies against kidney collecting duct cells. One of the patients developed autoantibodies targeting the collecting duct-specific water channel aquaporin 2, whereas autoantibodies of the two other patients reacted against the HOXB7 or NFAT5 transcription factors, which regulate the aquaporin 2 promoter. Our findings suggest that tubulointerstitial nephritis developed in these patients as a result of an autoimmune insult on the kidney collecting duct cells.

  • 18.
    Rosenqvist, Kerstin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Ebeling Barbier, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Nyman, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Treatment of acute portomesenteric venous thrombosis with thrombectomy through a transjugular intrahepatic portosystemic shunt: a single-center experience.2018Ingår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 59, nr 8, s. 953-958Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Acute portomesenteric venous thrombosis (PMVT) is a potentially life-threatening condition and urgent treatment is required.

    Purpose: To retrospectively evaluate the efficacy and safety of treating acute PMVT by the creation of a transjugular intrahepatic portosystemic shunt (TIPS) followed by thrombectomy.

    Material and Methods: Six patients (all men, age range = 39-51 years) presenting with acute PMVT were treated with transjugular thrombectomy (TT) through a TIPS created in the same session. The intervention included iterated venography through the TIPS one to three times within the first week after diagnosis and repeated thrombectomy if needed (n = 5).

    Results: Recanalization was successful with persistent blood flow through the main superior mesenteric vein, portal vein, and TIPS in all six patients. Five patients were treated primarily with thrombectomy through a TIPS with clinical improvement. The final patient was initially treated with surgical thrombectomy and bowel resection. TIPS and TT was performed two days after surgery due to re-thrombosis but the patient deteriorated and died of multi-organ failure. Procedure-related complications were transient hematuria (n = 3) and transient encephalopathy (n = 2). In-hospital time was <14 days in four of the five patients with primary TIPS and TT. No sign of re-thrombosis was noted during follow-up (mean = 18 months, range = 8-28 months).

    Conclusion: Thrombectomy through a TIPS is feasible and can be effective in recanalization and symptom-relief in acute PMVT.

  • 19.
    Rosenqvist, Kerstin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Eriksson, Lars-Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Nyman, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Endovascular treatment of acute and chronic portal vein thrombosis in patients with cirrhotic and non-cirrhotic liver2016Ingår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 57, nr 5, s. 572-579Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Treatment of patients with portal vein thrombosis (PVT) differs due to different etiology and wide range of symptoms but certain patients seems to benefit from endovascular intervention.

    PURPOSE: To assess the safety and efficiency of endovascular treatment of acute and chronic PVT in patients with cirrhotic and non-cirrhotic liver.

    MATERIAL AND METHODS: Twenty-one patients with PVT treated with an endovascular procedure in 2002-2013 were studied retrospectively. Data on etiology, onset and extension of thrombus, presenting symptoms, methods of intervention, portal pressure gradients, complications, recurrence of symptoms, re-interventions, clinical status at latest follow-up, and survival were collected.

    RESULTS: Four non-cirrhotic patients with acute extensive PVT and bowel ischemia were treated with local thrombolysis, in three combined with placement of a transjugular intrahepatic portosystemic shunt (TIPS) placement. Three recovered and have survived more than 6 years. In six non-cirrhotic patients with chronic PVT and acute or threatening variceal bleeding recanalization and TIPS were successful in three and failed in three. Eleven cirrhotic patients with PVT and variceal bleeding or refractory ascites were successfully treated with recanalization and TIPS. Re-intervention was performed in five of these patients and five patients died, three within 12 months of intervention. Four cirrhotic patients had episodes of shunt-related encephalopathy and three had variceal re-bleeding.

    CONCLUSION: TIPS was found to be effective in reducing portal hypertension in patients with PVT. In patients with extensive PVT and bowel ischemia treatment with TIPS combined with thrombolysis should be considered.

  • 20.
    Rosenqvist, Kerstin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sheikhi, Reza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Eriksson, Lars-Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Rajani, Rupesh
    Karolinska Univ Hosp, Dept Gastroenterol, Stockholm, Sweden.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Nyman, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Endovascular treatment of symptomatic Budd-Chiari syndrome - in favour of early transjugular intrahepatic portosystemic shunt.2016Ingår i: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 28, nr 6, s. 656-660Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Treatment of Budd-Chiari syndrome (BCS) has shifted from mainly medical treatment, with surgical shunt and orthotopic liver transplantation (OLT) as rescue, to medical treatment combined with an early endovascular intervention in the past two decades.

    PURPOSE: To assess the safety and efficiency of endovascular treatment of symptomatic patients with BCS and to compare mortality with symptomatic BCS patients in the same region treated with only sporadic endovascular techniques.

    METHODS: This was a retrospective review of clinical data, treatment and survival in 14 patients diagnosed with BCS and treated with endovascular methods from 2003 to 2015. A national epidemiology study of BCS from 1986 to 2003 was used for comparison.

    RESULTS: Thirteen of the 14 patients eventually had transjugular intrahepatic portosystemic shunt (TIPS), four after previous liver vein angioplasty. TIPS were performed with polytetrafluoroethylene-covered stents and technical success was 100%. Calculated preinterventional prognostic indices indicated a high risk of TIPS dysfunction, OLT and death. However, only one patient died and one had an OLT, and the 1- and 2-year primary TIPS-patency was 85 and 67%, respectively. Episodes of de-novo hepatic encephalopathy occurred in three patients. Overall 1- and 5-year transplantation-free survival was 100 and 93% compared with 47 and 28%, respectively, in 1986 to 2003.

    CONCLUSION: TIPS seems to be a safe and effective treatment for symptomatic BCS and there is an obvious improvement in transplantation-free survival compared with conservatory medical treatment. It should, therefore, be considered early, as first-line intervention, in patients with insufficient response to medical treatment.

  • 21.
    Rosenqvist, Kerstin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Sheikhi, Reza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Nyman, Rickard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sangfelt, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Ebeling Barbier, Charlotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Transjugular intrahepatic portosystemic shunt treatment of variceal bleeding in an unselected patient population.2018Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 1, s. 70-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) in variceal bleeding in a clinical setting.

    MATERIALS AND METHODS: Retrospective review of 131 patients (116 with liver cirrhosis) treated with TIPS with covered stent grafts in a single centre from 2002 to 2016.

    RESULTS: Survival at 1 and 2 years was 70% and 57% in patents with, and 100% at 2 years in patients without liver cirrhosis, respectively. A high Child-Pugh score and severe hepatic encephalopathy (HE) within 12 months post-TIPS were related to increased mortality. Re-bleeding occurred in 8% within 12 months and was related to TIPS dysfunction and a post-TIPS portosystemic gradient (PSG) of ≥5 mmHg. The main cause of TIPS dysfunction was that the stent did not fully reach the inferior vena cava. There was no correlation between the PSG and the occurrence of HE.

    CONCLUSIONS: TIPS was safe and prevented re-bleeding in patients with variceal bleeding, with or without liver cirrhosis, regardless of Child-Pugh class and of how soon after bleeding onset, the TIPS procedure was performed. A post-TIPS PSG of ≥5 mmHg was associated with an increased risk for re-bleeding and there was no correlation between the post-TIPS PSG and the occurrence of HE.

  • 22.
    Rönnblom, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Holmstrom, Tommy
    Tanghoj, Hans
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sjoberg, Daniel
    Appearance of hepatobiliary diseases in a population-based cohort with inflammatory bowel diseases (Inflammatory Bowel Disease Cohort of the Uppsala Region)2015Ingår i: Journal of Gastroenterology and Hepatology, ISSN 0815-9319, E-ISSN 1440-1746, Vol. 30, nr 8, s. 1288-1292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and AimTo prospectively follow the evolution of hepatobiliary diseases in a population-based cohort of patients with inflammatory bowel diseases. MethodsBetween 2005 and 2009, 790 incident cases of ulcerative colitis and Crohn's disease were registered in the Uppsala Health Region, corresponding to an average incidence of 20.0 and 9.9 new cases/100000 inhabitants/year, respectively. Liver function tests were analyzed in 97.1% and the results of ensuing investigations were summarized. ResultsSeventeen patients with primary sclerosing cholangitis were diagnosed corresponding to an overall prevalence of 2.2% (ulcerative colitis 1.7% and Crohn's disease 3.0%, respectively). The median age at diagnosis was 25 years (interquartile range: 17.0-34.0). Among the 92 patients below 17 years of age, three had autoimmune hepatitis and three primary sclerosing cholangitis, summing up to a prevalence of 6.5% immune-mediated hepatobiliary diseases among the pediatric patients. Three patients have undergone liver transplantation and one died of colonic carcinoma. Ten patients have demonstrated persistent elevation of alkaline phosphatases but had a normal magnetic resonance cholangiopancreatography (two patients) or refused further investigation (one patient). ConclusionIn this first large prospective population-based cohort of 526 patients with ulcerative colitis (UC) and 264 with Crohn's disease, 17 cases of primary sclerosing cholangitis were found, among whom three (17%) so far have been liver transplanted and one has died of colon carcinoma. The average age of those affected by primary sclerosing cholangitis is considerably lower than usually reported. Ten patients had or have had elevated alkaline phosphatase without confirmed liver or biliary disease.

  • 23.
    Sangfelt, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Wanders, Alkwin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Rasmussen, Ib
    Karlson, Britt-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Bergquist, Annika
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Monitoring Dominant Strictures in Primary Sclerosing Cholangitis with Brush Cytology and FDG-PET2014Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 61, nr 6, s. 1352-1357Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/AIMS: Despite high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed.

    METHOD: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [18F]fluorodeoxyglucose ([18F]FDG-PET/CT), measured as the maximum standardized uptake values normalized to the liver background (SUVmax/liver) at 180 minutes, in PSC patients with dominant bile duct strictures.

    RESULTS: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 56%, 89%, 75% and 88%, respectively. Preemptive liver transplantations due to repeated HGD before manifest CCA were performed in six patients. Receiver operating characteristic (ROC) analysis of [18F]FDG uptake showed that a SUVmax/liver quotient of 3.3 was able to discriminate between CCA and non-malignant disease with a sensitivity, specificity, PPV and NPV for CCA of 89%, 92%, 62%, 98%, respectively. A SUVmax/liver >3.3 detected CCA in 8/9 patients whereas a quotient < 2.4 excluded CCA. Combining brush cytology and quantitative [18F]FDG-PET/CT yielded a sensitivity for HGD and/or CCA of 100% and a specificity of 88%.

    CONCLUSION: Early detection of HGD before manifest CCA is feasible with repeated brush cytology and may allow for preemptive liver transplantation. [18F]FDG-PET/CT has a high sensitivity for manifest CCA and a negative scan indicates a non-malignant state of the disease. Brush cytology and [18F]FDG-PET/CT are complementary in monitoring and managing PSC patients with dominant strictures.

  • 24.
    Sköldberg, Filip
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Portela-Gomes, Guida M.
    Grimelius, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Nilsson, Gunnar
    Perheentupa, Jaakko
    Betterle, Corrado
    Husebye, Eystein S.
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells2003Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 88, nr 4, s. 1445-1452Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with autoimmune polyendocrine syndrome type 1 often have autoantibodies against neurotransmitter synthesizing enzymes, including the pyridoxal phosphate-dependent enzymes glutamic acid decarboxylase and aromatic L-amino acid decarboxylase. Using a candidate approach, we have identified the histamine-synthesizing enzyme histidine decarboxylase, also pyridoxal phosphate dependent, as an autoantigen in this disorder. Anti-histidine decarboxylase antibodies reacting with in vitro translated antigen were found in 36/97 (37%) of autoimmune polyendocrine syndrome type 1 patients studied. The antibodies also reacted with the native enzyme in HMC-1 cell lysates and did not cross-react with the highly homologous aromatic L-amino acid decarboxylase. Anti-histidine decarboxylase antibodies were associated with a history of intestinal dysfunction (P = 0.017). Gastric and duodenal biopsies from a patient with anti-histidine decarboxylase antibodies were studied by immunohistochemistry. The oxyntic mucosa was found to lack the histamine producing enterochromaffin-like cells, suggestive of an autoimmune destruction. To our knowledge, this is the first report of autoantibodies against histidine decarboxylase and absence of gastric enterochromaffin-like cells.

  • 25.
    Sköldberg, Filip
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Perheentupa, Jaakko
    Landin-Olsson, Mona
    Husebye, Eystein S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gustafsson, Jan
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease2004Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 89, nr 4, s. 1636-1640Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The structurally related group II pyridoxal phosphate (PLP)-dependent amino acid decarboxylases glutamic acid decarboxylase (GAD), aromatic L-amino acid decarboxylase (AADC), and histidine decarboxylase (HDC) are known autoantigens in endocrine disorders. We report, for the first time, the prevalence of serum autoantibody reactivity against cysteine sulfinic acid decarboxylase (CSAD), an enzyme that shares 50% amino acid identity with the 65- and 67-kDa isoforms of GAD (GAD-65 and GAD-67), in endocrine autoimmune disease. Three of 83 patients (3.6%) with autoimmune polyendocrine syndrome type 1 (APS1) were anti-CSAD positive in a radioimmunoprecipitation assay. Anti-CSAD antibodies cross-reacted with GAD-65, and the anti-CSAD-positive sera were also reactive with AADC and HDC. The low frequency of anti-CSAD reactivity is in striking contrast to the prevalence of antibodies against GAD-65, AADC, and HDC in APS1 patients, suggesting that different mechanisms control the immunological tolerance toward CSAD and the other group II decarboxylases. Moreover, CSAD may be a useful mold for the construction of recombinant chimerical antigens in attempts to map conformational epitopes on other group II PLP-dependent amino acid decarboxylases.

  • 26.
    Sköldberg, Filip
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Thornemo, M
    Lindahl, A
    Bird, PI
    Uppsala universitet.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Landgren, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Identification of AHNAK as a novel autoantigen in systemic lupuserythematosus2002Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 291, nr 4, s. 951-958Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To identify candidate autoantigens associated with arthritis, a rat chondrocyte cDNA library was immunoscreened with serum from a patient with rheumatoid arthritis. One isolated cDNA encoded part of AHNAK, a 700-kDa phosphoprotein with DNA binding properties, that appears to be involved in several signal transduction pathways. Immunoreactivity against an in vitro translated human AHNAK fragment was detected in 4.6% (5/109) of patients with rheumatoid arthritis, 29.5% (18/61) of patients with systemic lupus erythematosus (SLE), and 1.2% (2/172) of blood donors. Anti-AHNAK antibodies reacted with a recombinant human AHNAK fragment and with native AHNAK from C32 cell lysates. In vitro translated AHNAK fragment could be cleaved by granzyme B and caspase-3. Anti-AHNAK positive SLE patients had a higher frequency of homogeneous antinuclear antibody staining patterns and a lower frequency of recent mucosal ulcerations. This is the first report that AHNAK can be targeted by the immune system in autoimmune disease.

  • 27.
    Söderbergh, A
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, F
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Halonen, M
    Ekwall, O
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Björses, P
    Kämpe, O
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Husebye, E S
    Autoantibodies against aromatic L-amino acid decarboxylase identifies a subgroup of patients with Addison's disease2000Ingår i: J Clin Endocrinol Metab, ISSN 0021-972X, Vol. 85, s. 460-463Artikel i tidskrift (Övrigt vetenskapligt)
  • 28.
    Söderbergh, Annika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ekwall, Olov
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Hallgren, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nilsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rorsman, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Annerén, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Autoantibodies linked to autoimmune polyendocrine syndrome type I are prevalent in Down syndrome2006Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 95, nr 12, s. 1657-1660Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Patients with Down syndrome are prone to autoimmune diseases which also occur in the recessive disease autoimmune polyendocrine syndrome type I (APS I). Since this disease is caused by mutations in the gene AIRE on chromosome 21, one might speculate that altered expression of AIRE contributes to autoimmune disease in Down syndrome. AIM: To study the prevalence of 11 well-defined autoantibodies, five of which are specific for APS I, associated with various manifestations of APS I in patients with Down syndrome. METHODS: Sera from 48 patients with Down syndrome were analysed. Autoantibodies against 21-hydroxylase, 17alpha-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, cytochrome P4501A2, tyrosine hydroxylase, tryptophan hydroxylase, glutamic acid decarboxylase 65, tyrosine phosphatase IA-2 and transglutaminase were analysed using an immunoprecipitation assay, and thyroid peroxidase autoantibodies were measured using a haemagglutination assay. RESULTS: Seven of 48 patients had elevated titres of autoantibodies: one against 21-hydroxylase, three against aromatic L-amino acid decarboxylase, one against cytochrome P4501A2, one against glutamic acid decarboxylase 65 and one against tyrosine phosphatase IA-2. None of the patients had clinical or laboratory signs of disease coupled to the respective autoantibody. CONCLUSION: Four patients with Down syndrome had autoantibodies hitherto regarded as unique for APS I, which may suggest a dysregulation of AIRE.

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