Artikel
Mucosal plasmablasts as biomarkers in systemic sclerosis
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Autoren
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Georg Tilgner
- Deutsches Rheumaforschungszentrum Berlin, Charité – Universitätsmedizin Berlin, Rheumatologie und Immunologie, Berlin
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Qingyu Cheng
- Deutsches Rheuma-Forschungszentrum (DRFZ), Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Claudia Kedor
- Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Falk Hiepe
- Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Bimba Franziska Hoyer
- Sektion Rheumatologie/Zentrum für Entzündungsmedizin, Medizinische Klinik I, UKSH, Campus Kiel, Kiel
| Veröffentlicht: | 5. Februar 2019 |
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Gliederung
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Background: Systemic sclerosis (SSc) is a rare connective tissue disease affecting the skin, lung and gastro-intestinal tract (GI). Therapy is difficult and biomarkers for pulmonary or GI-involvement are lacking today. B cells and plasmablasts (PBs) play a major role in patients with Systemic Sclerosis. This finding is reflected in the presence of autoantibodies against CENP and Scl-70. Furthermore, B Cell depleting therapy seems to be effective.
Among others, Mei et al. revealed that a major part of human steady-state blood plasma cells have their origin in mucosal immune reactions, determined by their specific expression of IgA, CCR10 and α4β7-Integrin – markers for mucosal origin (Mei et al. 2009).
Based on those markers, the central aim of our study is to put alterations of the mucosal immune system into perspective with clinical symptoms of SSc patients.
Methods: 49 SSc patients (25 with limited Systemic Sclerosis and 20 with diffuse Systemic Sclerosis) were analysed by flow cytometry and compared to 23 healthy donors. The flow cytometry staining markers used to evaluate our hypothesis of over activated B cells in SSc are CD19, CD20, CD27, IgM, CD95, IgD, CD138, HLA-DR, IgA, CCR7, CCR10, β7-Integrin and CD62L.
Results: Marked differences (p=0,0085) were found regarding an increased frequency of IgA+ PBs in patients with SSc (median=59,3, n=46) as compared to healthy donors(HDs) (median=48, n=23)). Interestingly, this increase of IgA+ PB frequency is accentuated in patients with pulmonary fibrosis(PF) (median=66,1, n=21) as compared to patients without PF (median=57,2, n=22, p=0,08) and HDs (median=48, n=23, p=0,0024).
The frequency of PBs being positive for the mucosal marker α4β7-Integrin is significantly higher in SSc patients (median=44,65, n=46) in comparison with HDs (median=35,2, n=23) (p=0,0173). This increase of α4β7-Integrin positive PB frequency is again more pronounced in patients with PF (median=43,7, n=21) as compared to patients without PF (median=30,45, n=22, p=0,1585) and also increased in patients with pulmonary arterial hypertension(PAH) (median=59,9, n=10) in comparison to patients without PAH (median=43,6, n=33, p=0,0829).
Further clinical analyses indicates that α4β7-Integrin+IgA+ PBs might possess an increased resistance against B cell depletion therapy with Rituximab (RTX) based on the higher frequency of those cells patients after RTX treatment (median=65,5, n=3) as compared to patients without RTX treatment (median=38,55, n=46, p=0,0431) and HDs (median=22,4, n=23, p=0,0085).
Conclusion: The frequency of PBs with a mucosal phenotype is increased in patients with SSc. This increase of mucosal activity is partly associated with pulmonary involvement. PBs with a mucosal phenotype seem to have an increased resistance against B cell depleting therapy.
Those findings indicate that mucosal plasmablasts could serve as biomarkers in SSc and will help to develop further therapeutic strategies.
