Artikel
Elevated STAT1 levels by T and B cells but unaltered B cell distribution in asymptomatic anti-SSA positive women at-risk for congenital heart block
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Autoren
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Jacob Casimir Ritter
- Charité – Universitätsmedizin Berlin, Klinik für Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheumaforschungszentrum (DRFZ), Berlin
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Franziska Szelinski
- Charité – Universitätsmedizin Berlin, Klinik für Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheumaforschungszentrum (DRFZ), Berlin
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Arman Aue
- Deutsches Rheumaforschungszentrum (DRFZ), Berlin; Charité – Universitätsmedizin Berlin, Klinik für Nephrologie und Intensivmedizin, Berlin
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Ana-Luisa Stefanski
- Charité – Universitätsmedizin Berlin, Klinik für Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheumaforschungszentrum (DRFZ), Berlin
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Eva V. Schrezenmeier
- Deutsches Rheumaforschungszentrum (DRFZ), Berlin; Charité – Universitätsmedizin Berlin, Klinik für Nephrologie und Intensivmedizin, Berlin
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Andreia Lino
- Deutsches Rheumaforschungszentrum (DRFZ), Berlin
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Thomas Dörner
- Charité – Universitätsmedizin Berlin, Klinik für Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheumaforschungszentrum (DRFZ), Berlin
| Veröffentlicht: | 18. September 2024 |
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Gliederung
Text
Introduction: The presence of anti-SSA autoantibodies and type I interferon (IFN) are risk factors for the development of autoimmune congenital heart block (CHB) [1], [2]. While the effects have been documented in women diagnosed with Sjögren’s disease (SjD), the implications for asymptomatic women who harbor these antibodies (at-risk) remain less understood. Thus, there exists a necessity for a deeper understanding of potential IFN consequences and B cell abnormalities among those at-risk women.
Methods: Peripheral blood samples were obtained and permeabilized from anti-SSA+ healthy women (at-risk) (n=7, including three pregnancies with CHB), SjD patients (n=11) and healthy donors (HD) (n=21) for intracellular staining. T and B cell subsets were identified together with a comprehensive analysis of IFN signaling molecules using flow cytometry. Immune cell frequencies, signaling molecules and clinical data were subjected to statistical analyses.
Results: The at-risk group for CHB exhibited elevated Siglec-1 (CD169) levels, an IFN signature marker expressed by CD14+ monocytes, compared to healthy donors but similar to those found in SjD patients.
Importantly, STAT1 levels among all B cell subsets including naïve (CD27-IgD+), pre-switched (CD27+IgD+), switched-memory (CD27+IgD-), double negative (CD27-IgD-) B cells and in particular by plasmablasts (CD20lowCD27++) were elevated in the at-risk group compared to HD (Figure A [Fig. 1]). Importantly, STAT1 and IRF9 levels were elevated in CD4+ and CD8+ T cells in at-risk women compared to HD. There were no differences of STAT1, IRF9 levels among at-risk patients compared to patients with SjD.
Noteworthy, at-risk women presented with similar T and B cell frequencies as those in HD, while SjD patients exhibited an increase in naïve B cells and diminished memory B cell frequencies (Figure B [Fig. 1]).
Finally, there was a correlation between STAT1 and Siglec-1 (CD169) expression, especially in plasmablasts in the at-risk group.
Conclusion: Our data suggest increased transcriptional activity of type I IFN signaling molecules in T and B cell subsets among at-risk women and SjD patients producing anti-SSA antibodies. The molecular similarities between the at-risk lacking overt disease and the SjD cohorts (IFN and anti-SS-A signature) underscore the necessity for additional mechanistic studies on how increased type I IFN and B cell abnormalities translate into clinical disease.
References
- 1.
- Lisney AR, Szelinski F, Reiter K, Burmester GR, Rose T, Dörner T. High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block. Ann Rheum Dis. 2017 Aug;76(8):1476-80. DOI: 10.1136/annrheumdis-2016-210927
- 2.
- Brito-Zerón P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol. 2015 May;11(5):301-12. DOI: 10.1038/nrrheum.2015.29
