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  • 1.
    Dahlbom, I
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Olsson, M
    Forooz, NK
    Sjöholm, AG
    Truedsson, L
    Hansson, Tony
    Department of Rheumatology, Karolinska Institute.
    Immunoglobulin G (IgG) Anti-Tissue Transglutaminase Antibodies Used as Markers for IgA-Deficient Celiac Disease Patients.2005In: Clin Diagn Lab Immunol., Vol. 12, no 2, p. 254-258Article in journal (Refereed)
  • 2.
    Dahlbom, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Agardh, Daniel
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Protein A and protein G ELISA for the detection of IgG autoantibodies against tissue transglutaminase in childhood celiac disease2008In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 395, no 1-2, p. 72-6Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate if the detection of celiac disease (CD) in children was improved by using alternative conjugates for assessment of tissue transglutaminase (tTG) autoantibodies. Methods: Serum samples from 108 biopsy confirmed CD children and 42 control subjects were investigated for the presence of autoantibodies with tTG coated microplates using protein A (PA), protein G (PG), anti-IgG, or anti-IgA as conjugates. Results: Of the 108 CD children, 86 (80%) were IgG-tTG positive, 91 (84%) were positive with the PA-conjugate, 94 (87%) were positive with the PG-conjugate, and 103 (95%) were IgA-tTG positive. Among the 42 controls. 4 (10%) were IgG-tTG positive, 5 (12%) were positive with both the PA- and PG conjugates. whereas 3 (7%) were IgA-tTG positive. Compared with IgG-tTG the concordance was 93% for PA and 95% for PG, with a positive correlation between antibody levels (r=0.967 and r=0.975. p< ;0.0001). All but one CD child were found positive by combining IgG-tTG and IgA-tTG detection. Conclusions: The sensitivity of IgG-tTG detection with ELISA increased by protein A or protein G conjugates, whereas the specificity was reduced as compared with anti-IgG conjugate. The combined measurement of IgA-tTG and IgG-tTG still seems to be the optimal procedure when screening children for CD.

  • 3.
    Dahlbom, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Korponay-Szabó, Ilma R
    Kovács, Judit B
    Szalai, Zsuzsanna
    Mäki, Markku
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Prediction of clinical and mucosal severity of celiac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase2010In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 50, no 2, p. 140-146Article in journal (Refereed)
    Abstract [en]

    Objectives: We analysed whether the quantification of autoantibodies against tissue transglutaminase could be used to predict mucosal destruction and disease severity in patients with gluten sensitivity. Patients and Methods: One hundred seventy patients with coeliac disease (CD), comprising 52 children with severe malabsorption (group 1), 59 children with mild symptoms (group II), 59 adults (group III), 134 patients with dermatitis herpetiformis (DH), and 131 disease controls, were studied. Serial serum samples of patients in groups I and II on a gluten-free diet were also included. Serum levels of antibodies against recombinant tissue transglutaminase were determined with ELISA using standard curves for quantification of antibodies. Results: Immunoglobulin (Ig)A antibodies against tissue transglutaminase (IgA-TGA) were detected in all of the patients with CD and in 95% of the DH patients. The IgA-TGA and IgG-TGA levels were higher in group I (P < 0.001). The IgG-TGA levels and positivity rate in group I (100%)were higher than in group II (81%), group III (73%), and the DH group (67%). Elevated IgA-TGA and IgG-TGA levels in combination predicted a more severe small intestinal atrophy (P < 0.0001) with a specificity of 99% for Marsh IIIb-IIIc (flat) lesions. The kinetics of the IgA-TGA decrease during diet differed between groups I and II. Conclusions: High levels of IgA-TGA and IgG-TGA antibodies were associated with the grade of mucosal villous atrophy and a more severe clinical presentation. The combined measurement of IgA-TGA and IgG-TGA enables a noninvasive prediction of small intestinal villous atrophy with high accuracy, and may reduce the need for a biopsy in patients with suspected CD.

  • 4.
    Dahlbom, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Lidström, M.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Vilen, H.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Andersson, K.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Kritikos, D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Daily Assessments of Perceived Sensations in Obese and Non-Obese Children/Adolescents Using a New Mobile Application2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, p. 14-14Article in journal (Other academic)
  • 5.
    Dahlbom, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nyberg, Britt-Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Berntson, Lillemor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Simultaneous detection of IgA and IgG antibodies against tissue transglutaminase: The preferred pre-biopsy test in childhood celiac disease2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 3, p. 208-216Article in journal (Refereed)
    Abstract [en]

    Objectives: IgA antibodies against tissue transglutaminase (anti-TG2) is a reliable marker of celiac disease (CD). However, IgA-deficient patients are not identified and young children may lack IgA anti-TG2. Combined detection of IgA and IgG (IgA/IgG) against deamidated gliadin peptides (DGP) has shown a high diagnostic performance for untreated CD. Here we examined the utility of IgA/IgG anti-TG2, IgA/IgG anti-DGP and IgA/IgG against a mix of TG2 and DGP (anti-TG2/DGP) in finding CD among children.

    Methods: Serum antibodies against TG2, DGP, and TG2/DGP were determined with ELISA in 242 children referred to a paediatric gastroenterologist. Fifty had untreated CD verified by an intestinal biopsy and 192/242 children had other diseases than CD.

    Results: Forty-eight untreated CD children had increased IgA/IgG anti-TG2, 47/50 had increased IgA/IgG anti-DGP and 46/50 had increased IgA/IgG anti-TG2/DGP. One control subject had increased IgA/IgG anti-TG2 and IgA/IgG anti-TG2/DGP, whereas 7/192 control subjects had increased IgA/IgG anti-DGP. The IgA/IgG anti-TG2 assay had the best performance with a sensitivity of 96%, a specificity of 99.5% and the area under the ROC-curve was 0.996 (95% CI 0.992-1, p < 0.0001).

    Conclusions: Detection of one antibody is not sufficient when screening for untreated CD among children due to cases of IgA deficiency. The inclusion of DGP antigens in the IgA/IgG combination assays seems to affect the sensitivity and specificity negatively, whereas detection of IgA/IgG anti-TG2 has the potential of finding most untreated CD patients, including those with IgA deficiency.

  • 6.
    de Faire, Ulf
    et al.
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Su, Jun
    Hua, Xiang
    Frostegård, Anna
    Halldin, Mats
    Hellenius, Mai-Lis
    Wikström, Max
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Grönlund, Hans
    Frostegård, Johan
    Department of Medicine, Karolinska University Hospital, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: Effects on uptake of oxidized LDL in macrophages as a potential mechanism2010In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 34, no 2, p. 73-79Article in journal (Refereed)
    Abstract [en]

    Objective: We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL). Methods: From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up. Serum levels of IgM anti-PC was determined by ELISA. Anti-PC was extracted from pooled human IgM and the effect of anti-PC on the uptake of OxLDL was studied by FACScan. Results: Relative risks (RR) with 95% confidence intervals (Cl) by quartiles of anti-PC levels with quartile 4 set as the reference value (RR = 1.0) and adjusted for smoking, BMI, type 11 diabetes, hypercholesterolaemia, and high blood pressure yielded an excess risk for CVD only for those within the lowest quartile of anti-PC values with an RR of 1.37 (CI 0.87-2.16). However, for men stronger associations were noted with increasing multivariately adjusted RRs from quartile 4 to quartile 1. Subjects within quartile I (values below 29.7 U/ml) had a significantly increased RR of 1.96 (Cl 1.09-3.55). Further adjustments for hsCRP gave essentially the same results. No excess risk was noted for women. Specific anti-PC could be extracted from IgM and these antibodies inhibited macrophage uptake of OxLDL Conclusions: Low IgM anti-PC could be a novel risk marker for CVD among men. One possible mechanism could be inhibition of uptake of oxLDL in macrophages.

  • 7.
    Enroth, Stefan
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Johansson, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Gyllensten, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Prevalence and sensitization of atopic allergy and coeliac disease in the Northern Sweden Population Health Study2013In: International Journal of Circumpolar Health, ISSN 2242-3982, E-ISSN 2242-3982, Vol. 72, p. 21403-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Atopic allergy is effected by a number of environmental exposures, such as dry air and time spent outdoors, but there are few estimates of the prevalence in populations from sub-arctic areas.

    OBJECTIVE:

    To determine the prevalence and severity of symptoms of food, inhalation and skin-related allergens and coeliac disease (CD) in the sub-arctic region of Sweden. To study the correlation between self-reported allergy and allergy test results. To estimate the heritability of these estimates.

    STUDY DESIGN:

    The study was conducted in Karesuando and Soppero in Northern Sweden as part of the Northern Sweden Population Health Study (n=1,068). We used a questionnaire for self-reported allergy and CD status and measured inhalation-related allergens using Phadiatop, food-related allergens using the F×5 assay and IgA and IgG antibodies against tissue transglutaminase (anti-tTG) to indicate prevalence of CD.

    RESULTS:

    The prevalence of self-reported allergy was very high, with 42.3% reporting mild to severe allergy. Inhalation-related allergy was reported in 26.7%, food-related allergy in 24.9% and skin-related allergy in 2.4% of the participants. Of inhalation-related allergy, 11.0% reported reactions against fur and 14.6% against pollen/grass. Among food-related reactions, 14.9% reported milk (protein and lactose) as the cause. The IgE measurements showed that 18.4% had elevated values for inhalation allergens and 11.7% for food allergens. Self-reported allergies and symptoms were positively correlated (p<0.01) with age- and sex-corrected inhalation allergens. Allergy prevalence was inversely correlated with age and number of hours spent outdoors. High levels of IgA and IgG anti-tTG antibodies, CD-related allergens, were found in 1.4 and 0.6% of participants, respectively. All allergens were found to be significantly (p<3 e-10) heritable, with estimated heritabilities ranging from 0.34 (F×5) to 0.65 (IgA).

    CONCLUSIONS:

    Self-reported allergy correlated well with the antibody measurements. The prevalence of allergy was highest in the young and those working inside. Heritability of atopy and sensitization was high. The prevalence of CD-related autoantibodies was high and did not coincide with the self-reported allergy.

  • 8.
    Forslund, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Weghuber, D.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Paulmichl, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Zsoldos, F.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Widhalm, K.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Vheu, M. D.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Lagler, F.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Cadamuro, J.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Brunner, S.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Hofmann, J.
    Paracelsus Med Univ, Dept Paediat, Salzburg, Austria;Paracelsus Med Univ, Obes Res Unit, Salzburg, Austria.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Lidström, M.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Vilen, H.
    Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala Univ, Childrens Hosp, Uppsala, Sweden.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kristinsson, Hjalti
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Alderborn, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Exenatide Once Weekly Reduces Weight, Liver Fat And 2-Hour Postprandial Glucose In Obese Adolescents2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 470, p. 14-15Article in journal (Other academic)
  • 9.
    Frisk, G
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hansson, T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dahlbom, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tuvemo, T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    A unifying hypothesis on the development of type 1 diabetes and celiac disease: Gluten consumption may be a shared causative factor2008In: Medical Hypotheses, ISSN 0306-9877, E-ISSN 1532-2777, Vol. 70, no 6, p. 1207-1209Article in journal (Refereed)
    Abstract [en]

    This paper presents a hypothesis of the aetiology of the increasing incidence of type 1 diabetes (T1D). This together with the global increased incidence of celiac disease (CID) and that these increases cannot be explained by genetic factors suggest a common environmental factor for these two diseases. Even though enterovirus (EV) infections are believed to trigger T1D and gluten is the trigger of CD, the increasing intake of gluten containing products all over the world could be the trigger for both diseases directly and indirectly. It has been shown that the duration of exposure to gluten is related to the prevalence of T1D. It has also been shown that T1D patients at onset have an inflammatory reaction in the gut. Hence, early diagnose of CD followed by elimination of dietary gluten will lead to a decreased incidence of T1D.

  • 10.
    Gingnell, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lindholm, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hudecova, Miriam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Arnadottir, Ragnheidur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Patients with polycystic ovary syndrome have lower levels of IgM anti-phosphorylcholine antibodies than healthy women2011In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 27, no 7, p. 486-490Article in journal (Refereed)
    Abstract [en]

    Introduction. IgM antibodies against phosphorylcholine (IgM anti-PC) are natural autoantibodies, possibly exerting one of the atheroprotective functions of the immune system. Increased levels of these antibodies reduce the development of atherosclerosis in mice, and low levels of IgM anti-PC have been associated with increased risk for cardiovascular disease (CVD). This study compared levels of IgM anti-PC in women with polycystic ovary syndrome (PCOS, n = 111) and healthy controls (n = 79). Method. Levels of IgM anti-PC were measured with ELISA. Results. The median level of IgM anti-PC in patients with PCOS was not significantly different compared to control subjects. However, the proportion of patients with PCOS with low levels of IgM anti-PC, defined as number of individuals below the median level, was significantly higher than among healthy controls, p < 0.05. Patients with PCOS in the oldest age quintile had significantly lower level of IgM anti-PC than control subjects of similar age (p < 0.05) and younger women with PCOS (p < 0.01). Conclusion. Our results indicate that women with PCOS more frequently display below-median levels of IgM anti-PC than controls and older women with PCOS have lower median anti-PC levels. Further studies of how this finding translates into actual CVD risk in women with PCOS are needed.

  • 11.
    Hansson, Tony
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Dahlbom, I
    Pharmacia & Upjohn Diagnostics.
    Hall, J
    Holtz, A
    Elfman, L
    Dannaeus, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Klareskog, L
    Antibody reactivity against human and guinea pig tissue transglutaminase in children with celiac disease2000In: J Pediatric Gastroenterology and Nutrition, Vol. 30, p. 379-Article in journal (Refereed)
  • 12.
    Hansson, Tony
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Tuvemo, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Frisk, Gun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Silent coeliac disease is over-represented in children with type 1 diabetes and their siblings2015In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 2, p. 185-191Article in journal (Refereed)
    Abstract [en]

    AimThis study measured autoantibodies against tissue transglutaminase (anti-tTG) to detect untreated coeliac disease in children with type 1 diabetes and their siblings. MethodsAnti-tTG was measured in prospectively collected sera from 169 children at the onset of diabetes, 88 of their siblings and 96 matched control children. Coeliac disease was confirmed with a small intestinal biopsy. ResultsCoeliac disease was diagnosed in five children before diabetes onset. A further 12 children were diagnosed after diabetes onset, without any gastrointestinal symptoms, and 11 of these had anti-tTG at the onset of diabetes, with the remaining child showing seroconversion within 6months. Hence, all the children with both diseases had anti-tTG at or before diabetes diagnosis, and the prevalence of coeliac disease was 10.1%. Moreover, 6.8% of the siblings and 3.1% of the control children had elevated levels of anti-tTG. None of the siblings reported any coeliac-related symptoms, despite being positive for anti-tTG, and coeliac disease has so far been biopsy confirmed in 4.5%. ConclusionSilent coeliac disease is over-represented in children with type 1 diabetes and their siblings. All diabetes children and their siblings should be tested and followed for the presence of anti-tTG and coeliac disease.

  • 13. Hansson, Tony
    et al.
    Ulfgren, AK
    Lindroos, E
    DannAEus, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dahlbom, I
    Pharmacia Diagnostics.
    Klareskog, L
    Transforming growth factor-beta (TGF-beta) and tissue transglutaminaseexpression in the small intestine in children with coeliac disease.2002In: Scand J Immunol, Vol. 56, p. 530-Article in journal (Refereed)
  • 14. Korponay-Szabó, I R
    et al.
    Dahlbom, I
    Pharmacia Diagnostics.
    Laurila, K
    Koskinen, S
    Woolley, N
    Partanen, J
    Kovács, J B
    Mäki, M
    Hansson, Tony
    Department of Rheumatology.
    Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency2003In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 52, no 11, p. 1567-1671Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult.

    AIMS: To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies.

    PATIENTS: We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors.

    METHODS: IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections.

    RESULTS: The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles.

    CONCLUSIONS: IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.

  • 15.
    Lagerqvist, Carina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Jidell, Erik
    Juto, Per
    Olcén, Per
    Stenlund, Hans
    Hernell, Olle
    Ivarsson, Anneli
    Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age2008In: Journal of Pediatric Gastroenterology and Nutrition - JPGN, ISSN 0277-2116, E-ISSN 1536-4801, Vol. 47, no 4, p. 428-35Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim was to investigate age-dependent serum levels and occurrence of elevated celiac disease (CD)-related antibodies in young children, to define the optimal serological procedure when selecting for small intestinal biopsy. PATIENTS AND METHODS: Included were 428 children with biopsy verified CD (median age 16 months; range 7.5 months-14 years) and 216 controls (median age 2.7 years; range 8.5 months-14.6 years). Immunoglobulin (Ig) A antibodies against gliadin (AGA-IgA), tissue transglutaminase (tTG-IgA), and endomysium (EMA-IgA) were analysed. RESULTS: Increased serum AGA-IgA levels were found in 411 of 428 CD cases, tTG-IgA in 385 of 428, and EMA-IgA in 383 of 428. In the control group, 11 of 216 had increased levels of AGA-IgA, 5 of 216 of tTG-IgA, and 8 of 216 of EMA-IgA. In CD children younger than 18 months, elevated AGA-IgA occurred in 97% and elevated tTG-IgA and EMA-IgA were found in 83% of the cases. Conversely, in CD children older than 18 months, elevated AGA-IgA occurred in 94%, and elevated tTG-IgA and EMA-IgA were found in 99% of the cases. CONCLUSIONS: In children older than 18 months, both tTG-IgA and EMA-IgA are sufficiently accurate to be used as a single antibody marker, whereas a large proportion of younger children with CD lack these antibodies. Therefore, when selecting children for small intestinal biopsy, the detection of a combination of AGA-IgA and tTG-IgA is optimal for identifying untreated CD in children younger than 18 months.

  • 16.
    Lindholm, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Blomquist, Caroline
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden.
    Bixo, Marie
    Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Sweden.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Hansson, Tony
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Burén, Jonas
    Department of Public Health and Clinical Medicine, Umeå University Hospital, Sweden.
    No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls2011In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 26, no 6, p. 1478-1485Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have indicated that peripheral circulating markers of inflammation are elevated in women with polycystic ovary syndrome (PCOS), but thus far no studies concerning markers of inflammation in adipose tissue have been published. The aim of the study was to investigate whether patients with PCOS display increased expression of inflammatory markers in adipose tissue.

    Methods: Twenty overweight patients with PCOS, 10 lean patients with PCOS and 20 overweight controls had subcutaneous fat biopsies and blood samples taken. Adipose tissue levels of mRNA of inflammatory markers were determined by use of real-time PCR.

    Results: Overweight patients with PCOS had higher relative adipose tissue chemokine ligand 2 (P < 0.01), and its cognate receptor (P < 0.05), tumour necrosis factor-alpha (P < 0.001), interleukin (IL)-10 (P < 0.001) and IL-18 (P < 0.001) and the monocyte/ macrophage markers CD14 (P < 0.01) and CD163 (P < 0.01) mRNA levels compared with lean women with PCOS. There were no differences between overweight patients with PCOS and overweight control subjects in this respect. Within the PCOS group, markers of adipose tissue inflammation correlated significantly with obesity-related metabolic disturbances, but when data were adjusted for age and BMI, most correlations were lost.

    Conclusions: Overweight, rather than the PCOS diagnosis per se, appears to be the main explanatory variable for elevated adipose tissue inflammation in patients with PCOS.

  • 17. Midhagen, G
    et al.
    Aberg, A-K
    Olcén, P
    Järnerot, G
    Valdimarsson, T
    Dahlbom, I
    Pharmacia Diagnostics.
    Hansson, Tony
    Department of Rheumatology, Karolinska Institute.
    Ström, M
    Antibody levels in adult patients with coeliac disease during gluten-free diet: a rapid initial decrease of clinical importance2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 6Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Analysis of antibodies against tissue transglutaminase (tTG) has been shown valuable in the diagnosis of coeliac disease (CD) but how quickly serum titres decrease after introduction of a gluten-free diet (GFD) is not known in adults. CD is a well-recognized disorder amongst the general population and many persons try a GFD for fairly vague symptoms before they seek medical advice. Therefore, it is important to determine the time that the serologic tests remain predictive of the disease after the introduction of a GFD.

    METHODS: Sera were taken from 22 consecutively biopsy-proven adult patients with CD in connection with the diagnostic biopsy. The patients were followed for 1 year and sera were taken after 1, 3, 6 and 12 months after start of a GFD. Sera were stored at -20 degrees C and analysed for IgA antibodies against gliadin, endomysium and two different commercial tTG assays based on recombinant human tTG (tTGrh) and guinea-pig liver (tTGgp).

    RESULTS: Twenty patients could be followed during GFD and all antibody titres fell sharply within 1 month after introduction of a GFD and continued to decline during the survey interval. Thirty days after beginning the diet only 58, 84, 74 and 53% of all patients had positive antibody levels of tTGrh, tTGgp, EmA and AGA respectively.

    CONCLUSIONS: As the antibodies used to confirm the diagnosis of CD fall rapidly and continue to decline following the introduction of a GFD, it is important that health care providers carefully inquire about the possibility of self-prescribed diets before patients sought medical attention.

  • 18. Mäki, Markku
    et al.
    Mustalahti, Kirsi
    Kokkonen, Jorma
    Kulmala, Petri
    Haapalahti, Mila
    Karttunen, Tuomo
    Ilonen, Jorma
    Laurila, Kaija
    Dahlbom, Ingrid
    Pharmacia Diagnostics.
    Hansson, Tony
    Pharmacia Diagnostics.
    Höpfl, Peter
    Knip, Mikael
    Prevalence of Celiac disease among children in Finland2003In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 348, no 25, p. 2517-2524Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that positive findings correlate with specific HLA haplotypes.

    METHODS: Serum samples were collected from 3654 students (age range, 7 to 16 years) in 1994 and screened in 2001 for endomysial and tissue transglutaminase antibodies. HLA typing was also performed on stored blood samples. All antibody-positive subjects were asked to undergo small-bowel biopsy in 2001.

    RESULTS: Of the 3654 subjects, 56 (1.5 percent) had positive antibody tests, as determined in 2001. Results of the two antibody tests were highly concordant. As of 1994, none of the subjects had received a clinical diagnosis of celiac disease, but 10 who had positive tests for both antibodies in serum obtained in 1994 received the diagnosis between 1994 and 2001. Of the 36 other subjects with positive antibody assays who agreed to undergo biopsy in 2001, 27 had evidence of celiac disease on biopsy. Thus, the estimated biopsy-proved prevalence was 1 case in 99 children. All but two of the antibody-positive subjects had either the HLA-DQ2 or the HLA-DQ8 haplotype. The prevalence of the combination of antibody positivity and an HLA haplotype associated with celiac disease was 1 in 67.

    CONCLUSIONS: The presence of serum tissue transglutaminase and endomysial autoantibodies is predictive of small-bowel abnormalities indicative of celiac disease. There is a good correlation between autoantibody positivity and specific HLA haplotypes. We estimate that the prevalence of celiac disease among Finnish schoolchildren is at least 1 case in 99 children.

  • 19.
    Paulmichl, K.
    et al.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Brunner, S.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria;PMU, Univ Hosp Salzburg, Ctr Expertise THERAPEP, Salzburg, Austria.
    Cadamuro, J.
    PMU, Univ Hosp Salzburg, Dept Med Chem Lab Diagnost, Salzburg, Austria.
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Nasemann, J.
    Roomp, K.
    Univ Luxembourg, Luxembourg Ctr Syst Biomed, Luxembourg, Luxembourg.
    Widhalm, K.
    Zsoldos, F.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.
    Weghuber, D.
    PMU, Univ Hosp Salzburg, Dept Pediat, Salzburg, Austria;PMU, Univ Hosp Salzburg, Obes Res Unit, Salzburg, Austria.
    Association Between Non-Alcoholic Fatty Liver Disease (NAFLD) and Iron Metabolism in Obese Children and Adolescents: Results of the Beta-JUDO Study2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no S470, p. 13-13Article in journal (Other academic)
  • 20. Simon-Vecsei, Zsofia
    et al.
    Kiraly, Robert
    Bagossi, Peter
    Toth, Boglarka
    Dahlbom, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Caja, Sergio
    Csosz, Eva
    Lindfors, Katri
    Sblattero, Daniele
    Nemes, Eva
    Maki, Markku
    Fesus, Laszlo
    Korponay-Szabo, Ilma R.
    A single conformational transglutaminase 2 epitope contributed by three domains is critical for celiac antibody binding and effects2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 2, p. 431-436Article in journal (Refereed)
    Abstract [en]

    The multifunctional, protein cross-linking transglutaminase 2 (TG2) is the main autoantigen in celiac disease, an autoimmune disorder with defined etiology. Glutamine-rich gliadin peptides from ingested cereals, after their deamidation by TG2, induce T-lymphocyte activation accompanied by autoantibody production against TG2 in 1-2% of the population. The pathogenic role and exact binding properties of these antibodies to TG2 are still unclear. Here we show that antibodies from different celiac patients target the same conformational TG2 epitope formed by spatially close amino acids of adjacent domains. Glu153 and 154 on the first alpha-helix of the core domain and Arg19 on first alpha-helix of the N-terminal domain determine the celiac epitope that is accessible both in the closed and open conformation of TG2 and dependent on the relative position of these helices. Met659 on the C-terminal domain also can cooperate in antibody binding. This composite epitope is disease-specific, recognized by antibodies derived from celiac tissues and associated with biological effects when passively transferred from celiac mothers into their newborns. These findings suggest that celiac antibodies are produced in a surface-specific way for which certain homology of the central glutamic acid residues of the TG2 epitope with deamidated gliadin peptides could be a structural basis. Monoclonal mouse antibodies with partially overlapping epitope specificity released celiac antibodies from patient tissues and antagonized their harmful effects in cell culture experiments. Such antibodies or similar specific competitors will be useful in further functional studies and in exploring whether interference with celiac antibody actions leads to therapeutic benefits.

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