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Lampinen, Maria
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Publications (10 of 29) Show all publications
Lampinen, M., Vessby, J., Fredricsson, A., Wanders, A., Rorsman, F. & Carlson, M. (2019). High serum sCD40 and a distinct colonic T cell profile in ulcerative colitis associated with primary sclerosing cholangitis.. Journal of Crohn's & Colitis, 13(3), 341-350
Open this publication in new window or tab >>High serum sCD40 and a distinct colonic T cell profile in ulcerative colitis associated with primary sclerosing cholangitis.
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2019 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, no 3, p. 341-350Article in journal (Refereed) Published
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.

National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-365803 (URN)10.1093/ecco-jcc/jjy170 (DOI)000464942000011 ()30383225 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Society of MedicineStiftelsen Olle Engkvist Byggmästare
Available from: 2018-11-14 Created: 2018-11-14 Last updated: 2019-05-09Bibliographically approved
Amcoff, K., Cao, Y., Zhulina, Y., Lampinen, M., Halfvarson, J. & Carlson, M. (2019). Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease. Scandinavian Journal of Gastroenterology, 54(10), 1237-1244
Open this publication in new window or tab >>Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 10, p. 1237-1244Article in journal (Refereed) Published
Abstract [en]

Background: Non-invasive markers for predicting relapse would be a useful tool for the management of patients with inflammatory bowel disease. Eosinophil granulocytes and their granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) have previously been shown to reflect disease activity in Crohn's disease and ulcerative colitis.

Aim: To examine the capacity of faecal ECP and EDN to predict relapse in ulcerative colitis and Crohn's disease, and to compare these proteins with faecal calprotectin.

Methods: Patients with Crohn's disease (n?=?49) and ulcerative colitis (n?=?55) were followed prospectively until relapse or end of the two-year study period. Faecal samples were obtained every third month. The predictive value of ECP and EDN was assessed in Cox regression models.

Results: In ulcerative colitis, a doubled EDN or ECP concentration was associated with a 31% and 27% increased risk of relapse, respectively. EDN levels were increased both at relapse and three months prior. By contrast, in Crohn's disease, the concentration of EDN was higher among patients in remission than in those who relapsed. Correlations between faecal calprotectin, ECP and EDN were observed in both diseases.

Conclusions: We demonstrate that the risk of relapse in ulcerative colitis can be predicted by consecutively measuring faecal EDN every third month, and suggest EDN as a complementary faecal marker to calprotectin to predict future relapse in ulcerative colitis. Our finding of higher EDN in Crohn's disease-patients staying in remission than in those who relapsed indicates different functions of the protein in ulcerative colitis and Crohn's disease.

Keywords
Inflammatory bowel disease, Crohn's disease, ulcerative colitis, biomarkers, eosinophils, inflammation
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-399012 (URN)10.1080/00365521.2019.1670251 (DOI)000488503800001 ()31577465 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RB13-0160Swedish Research Council, 521-2011-2764
Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-16Bibliographically approved
Lampinen, M., Fredricsson, A., Vessby, J., Martinez, J. F., Wanders, A., Rorsman, F. & Carlson, M. (2018). Downregulated eosinophil activity in ulcerative colitis with concomitant primary sclerosing cholangitis. Paper presented at 10th Biennial Symposium of the International-Eosinophil-Society, JUL 19-23, 2017, Gothenburg, SWEDEN. Journal of Leukocyte Biology, 104(1), 173-183
Open this publication in new window or tab >>Downregulated eosinophil activity in ulcerative colitis with concomitant primary sclerosing cholangitis
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2018 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 104, no 1, p. 173-183Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
eotaxin-1, flow cytometry, IL-33, proximity extension assay
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-358268 (URN)10.1002/JLB.3MA0517-175R (DOI)000435944300016 ()29603385 (PubMedID)
Conference
10th Biennial Symposium of the International-Eosinophil-Society, JUL 19-23, 2017, Gothenburg, SWEDEN
Funder
Stiftelsen Olle Engkvist Byggmästare
Available from: 2018-08-29 Created: 2018-08-29 Last updated: 2018-11-28Bibliographically approved
Amcoff, K., Cao, Y., Zhulina, Y., Lampinen, M., Halfvarson, J. & Carlson, M. (2018). Prognostic significance of eosinophil granule proteins in inflammatory bowel disease. Journal of Crohn's & Colitis, 12, S181-S182
Open this publication in new window or tab >>Prognostic significance of eosinophil granule proteins in inflammatory bowel disease
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S181-S182Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-357063 (URN)000427318900292 ()
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Moshkovits, I., Reichman, H., Karo-Atar, D., Rozenberg, P., Zigmond, E., Haberman, Y., . . . Munitz, A. (2017). A key requirement for CD300f in innate immune responses of eosinophils in colitis. Mucosal Immunology, 10(1), 172-183
Open this publication in new window or tab >>A key requirement for CD300f in innate immune responses of eosinophils in colitis
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2017 (English)In: Mucosal Immunology, ISSN 1933-0219, E-ISSN 1935-3456, Vol. 10, no 1, p. 172-183Article in journal (Refereed) Published
Abstract [en]

Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. Wehave recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f (-/-) mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f (-/-) mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-319892 (URN)10.1038/mi.2016.37 (DOI)000395807400017 ()27118491 (PubMedID)
Available from: 2017-04-10 Created: 2017-04-10 Last updated: 2017-11-29Bibliographically approved
Amcoff, K., Stridsberg, M., Lampinen, M., Magnuson, A., Carlson, M. & Halfvarson, J. (2017). Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time. Scandinavian Journal of Gastroenterology, 52(3), 344-350
Open this publication in new window or tab >>Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
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2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed) Published
Abstract [en]

Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Buhlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Buhlmann 845 (1061-226) g/g versus 62 (224-39) g/g, Phadia 369 (975-122) g/g versus 11 (52-11) g/g, and Immundiagnostik 135 (302-69) g/g versus 8 (56-4) g/g. The Buhlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Buhlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50g/g was used, whereas the differences in sensitivity were less pronounced.Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

Keywords
Biomarker, Crohn's disease, faecal calprotectin, inflammatory bowel disease, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-316426 (URN)10.1080/00365521.2016.1256424 (DOI)000392488800015 ()27881032 (PubMedID)
Funder
Swedish Research Council, 521-2011-2764
Available from: 2017-03-01 Created: 2017-03-01 Last updated: 2017-11-29Bibliographically approved
Hagforsen, E., Lampinen, M., Paivandy, A., Weström, S., Velin, H., Öberg, S., . . . Rollman, O. (2017). Siramesine causes preferential apoptosis of mast cells in skin biopsies from psoriatic lesions. British Journal of Dermatology, 177(1), 179-187
Open this publication in new window or tab >>Siramesine causes preferential apoptosis of mast cells in skin biopsies from psoriatic lesions
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2017 (English)In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 177, no 1, p. 179-187Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Skin mast cells are implicated as detrimental effector cells in various inflammatory skin diseases such as contact eczema, atopic dermatitis and psoriasis. Selective reduction of cutaneous mast cells, e.g. by inducing targeted apoptosis, might prove a rational and efficient therapeutic strategy in dermatoses negatively influenced by mast cells.

OBJECTIVES: The objective of the present study was to evaluate whether a lysosomotropic agent such as siramesine can cause apoptosis of mast cells present in psoriatic lesions.

MATERIALS AND METHODS: Punch biopsies were obtained from lesional and uninvolved skin in 25 patients with chronic plaque psoriasis. After incubation with siramesine, the number of tryptase-positive mast cells and their expression of interleukin (IL)-6 and IL-17 was analysed. Skin biopsies were digested to allow flow cytometric analysis of the drug's effect on cutaneous fibroblasts and keratinocytes.

RESULTS: Siramesine caused a profound reduction in the total number of mast cells in both lesional and uninvolved psoriatic skin biopsies without affecting the gross morphology of the tissue. The drug reduced the density of IL-6- and IL-17-positive mast cells, and showed antiproliferative effects on epidermal keratinocytes but had no apparent cytotoxic effect on keratinocytes or dermal fibroblasts.

CONCLUSIONS: Considering the pathophysiology of psoriasis, the effects of siramesine on cutaneous mast cells may prove favourable from the therapeutic aspect. The results encourage further studies to assess the usefulness of siramesine and other lysosomotropic agents in the treatment of cutaneous mastocytoses and inflammatory skin diseases aggravated by dermal mast cells.

National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-340992 (URN)10.1111/bjd.15336 (DOI)28117878 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Heart Lung Foundation
Available from: 2018-02-05 Created: 2018-02-05 Last updated: 2019-12-19Bibliographically approved
Lampinen, M., Fredricsson, A., Vessby, J., Wanders, A., Rorsman, F. & Carlson, M. (2016). 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 inflammation. Journal of Crohn's & Colitis, 10, S109-S109
Open this publication in new window or tab >>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 inflammation
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2016 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, p. S109-S109Article in journal, Meeting abstract (Other academic) Published
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-299652 (URN)000374496600160 ()
Available from: 2016-07-25 Created: 2016-07-25 Last updated: 2017-11-28Bibliographically approved
Hagforsen, E., Paivandy, A., Lampinen, M., Weström, S., Calounova, G., Melo, F. R., . . . Pejler, G. (2015). Ablation of human skin mast cells in situ by lysosomotropic agents. Experimental dermatology, 24(7), 516-521
Open this publication in new window or tab >>Ablation of human skin mast cells in situ by lysosomotropic agents
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2015 (English)In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 24, no 7, p. 516-521Article in journal (Refereed) Published
Abstract [en]

Mast cells are known to have a detrimental impact on numerous types of inflammatory skin diseases such as contact dermatitis, atopic eczema and cutaneous mastocytosis. Regimens that dampen skin mast cell-mediated activities can thus offer an attractive therapeutic option under such circumstances. As mast cells are known to secrete a large array of potentially pathogenic compounds, both from preformed stores in secretory lysosomes (granules) and after de novo synthesis, mere inhibition of degranulation or interference with individual mast cell mediators may not be sufficient to provide an effective blockade of harmful mast cell activities. An alternative strategy may therefore be to locally reduce skin mast cell numbers. Here, we explored the possibility of using lysosomotropic agents for this purpose, appreciating the fact that mast cell granules contain bioactive compounds prone to trigger apoptosis if released into the cytosolic compartment. Based on this principle, we show that incubation of human skin punch biopsies with the lysosomotropic agents siramesine or Leu-Leu methyl ester preferably ablated the mast cell population, without causing any gross adverse effects on the skin morphology. Subsequent analysis revealed that mast cells treated with lysosomotropic agents predominantly underwent apoptotic rather than necrotic cell death. In summary, this study raises the possibility of using lysosomotropic agents as a novel approach to targeting deleterious mast cell populations in cutaneous mastocytosis and other skin disorders negatively influenced by mast cells.

Keywords
apoptosis, LLME, lysosomotropic agents, mast cells, siramesine
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-258753 (URN)10.1111/exd.12699 (DOI)000356693000009 ()25808581 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Heart Lung Foundation
Available from: 2015-07-21 Created: 2015-07-20 Last updated: 2017-12-04Bibliographically approved
Karlsson, M., Linton, L., Lampinen, M., Karlen, P., Glise, H., Befrits, R., . . . Eberhardson, M. (2014). Naive T cells correlate with mucosal healing in patients with inflammatory bowel disease. Scandinavian Journal of Gastroenterology, 49(1), 66-74
Open this publication in new window or tab >>Naive T cells correlate with mucosal healing in patients with inflammatory bowel disease
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2014 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 49, no 1, p. 66-74Article in journal (Refereed) Published
Abstract [en]

Background. In previous studies, adaptive immune responses involving T-helper cells have been shown to play an important role in inflammatory bowel diseases (IBDs). Methods. The aim of this study was to investigate any correlation between the degree of mucosal inflammation and the phenotype of gut-infiltrating T-helper cells. Biopsies from intestinal mucosa were obtained and intestinal T cells were analyzed with regard to activity and maturation markers. Patients with active colitis (39 with Crohn's disease and 47 with ulcerative colitis) were included and treated with corticosteroids, biologicals or leukocytapheresis. Flow cytometry was used to analyze activation marker expression on gut-infiltrating T-helper cells. Results. Mucosal healing was reflected by almost 100% increase of CD62L expression in mucosal T cells in patients in remission compared to those with active inflammation (p < 0.01). The frequency of mucosal-naive CD4(+)CD45RA(+)T cells was reduced by 50% in mucosa displaying remission (5.3% compared to 12% of the total amount and CD4(+) T cells, p < 0.001). Surprisingly, the proportion of early activated T-helper cells (CD4(+)CD69(+)) did not differ between mucosa in remission and non-remission (43% and 42%, respectively). Moreover, no change in memory T-helper cells (CD4(+)CD45RO(+)) was observed (64% compared to 66%). The findings were independent of diagnosis (Crohn's disease or ulcerative colitis) or mode of treatment. Conclusion. This study suggests that a reduced recruitment of naive T-helper cells and increased frequency of T-helper cells with lymph node homing marker expression reflect mucosal healing in IBD. Surprisingly, the degree of activation of mucosal T-helper cells did not correlate with disease remission.

Keywords
flow cytometry, inflammatory bowel disease, mucosal healing, T cells
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-216739 (URN)10.3109/00365521.2013.853829 (DOI)000328948600009 ()
Available from: 2014-01-27 Created: 2014-01-24 Last updated: 2017-12-06Bibliographically approved
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