Artikel
Abnormalities of type I and type II Interferon signalling in B cells in primary Sjögren’s syndrome were associated to subgroups with elevated serological activity
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Autoren
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Jacob Casimir Ritter
- Charité – Universitätsmedizin Berlin, Berlin; Charité – Campus Mitte Medizinische Klinik – Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Franziska Szelinski
- Charité – Universitätsmedizin Berlin, Berlin; Charité – Campus Mitte Medizinische Klinik – Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Arman Aue
- Charité – Universitätsmedizin Berlin, Berlin; Klinik für Nephrologie und internistische Intensivmedizin der Charité Berlin, Berlin
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Ana-Luisa Stefanski
- Charité – Universitätsmedizin Berlin, Berlin; Charité – Campus Mitte Medizinische Klinik – Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
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Eva Schrezenmeier
- Charité – Universitätsmedizin Berlin, Berlin; Klinik für Nephrologie und internistische Intensivmedizin der Charité Berlin, Berlin
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Thomas Dörner
- Charité – Universitätsmedizin Berlin, Berlin; Charité – Campus Mitte Medizinische Klinik – Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
| Veröffentlicht: | 31. August 2022 |
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Gliederung
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Introduction: B cell hyperactivity [1], manifested by autoantibody production (anti-SS-A, anti-SS-B) and hypergammaglobulinaemia as well as interferon (IFN) signature [2] play a central role in the pathogenesis of primary Sjögren’s Syndrome (pSS). The link between these hallmarks is still elusive. An improved understanding of IFN and JAK/STAT signalling on B cells may hold promise to improve potential treatment targets and related biomarkers for specific pSS subgroups.
Methods: Peripheral blood from 45 pSS patients and 35 healthy controls (HC) was obtained and permeabilized for intracellular staining. Here B and T cell markers were applied together with Signal Transducers and Activators of Transcription 1 (STAT1), STAT2, pSTAT1 and 2, Interferon Regulatory factor 9 (IRF9), IRF7 and IRF1 and analysed by using flow cytometry. Cell subsets and correlations with all markers and clinical information were subjected to statistical analyses.
Results: Compared to HC the pSS group showed significantly elevated STAT1 expression among all B cell subsets (p>0.0001) including naïve (CD27-IgD+), pre-switched (CD27+ IgD+), switched-memory (CD27+IgD-), double negative (CD27- IgD-) B cells and plasmablasts (CD27++ CD38++). Furthermore, IRF9 and STAT2 were increased among most B cell subsets.
Positive correlations were found between STAT1 and IRF9 with Siglec-1 (CD169), an IFN signature marker expressed on the surface of CD14+ monocytes (p>0.0001; r=0.633). Notably, increased levels of IRF9 positively correlates with STAT1.
Upregulated STAT1 and IRF9 within pSS B cells were associated to subgroups of patients especially with high anti-SS-A and anti-SS-B autoantibodies, high anti-nuclear antibody titers (ANA) and high rheumatoid factors (IgA, IgM).
Conclusion: The current data provide evidence of type I and type II IFN on B cell subsets in pSS. Elevated STAT1, STAT2 and IRF9 expression suggest transcriptionally activity, which was evident in pSS subgroups with extraglandular manifestations and elevated serologic activity.
Targeting JAK/STAT in pSS could be beneficial for patients with high STAT1 levels leading to a personalized approach for this specific subgroup of patients.
References
- 1.
- Nocturne G, Mariette X. B cells in the pathogenesis of primary Sjögren syndrome. Nat Rev Rheumatol. 2018 Mar;14(3):133-45. DOI: 10.1038/nrrheum.2018.1
- 2.
- Brkic Z, Maria NI, van Helden-Meeuwsen CG, van de Merwe JP, van Daele PL, Dalm VA, Wildenberg ME, Beumer W, Drexhage HA, Versnel MA. Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syndrome and association with disease activity and BAFF gene expression. Ann Rheum Dis. 2013 May;72(5):728-35. DOI: 10.1136/annrheumdis-2012-201381
