Artikel
Enrichment of phospholipid-reactive B cells among atypical memory subsets in APS patients
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Autoren
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Eduard Nitschke
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Eva V. Schrezenmeier
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin; Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité Campus Mitte, Berlin
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Ana-Luisa Stefanski
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Tobias Alexander
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Yidan Chen
- Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Thomas Dörner
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin
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Van Duc Dang
- Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin; University of Science, Vietnam National University Hanoi, Hanoi
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Hector Rincon-Arevalo
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin; Universidad de Antioquia, Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Instituto de Investigaciones Médicas, Medellín
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Jacob Casimir Ritter
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Jose-Bernardino Gonzalez
- Labor Berlin – Charité Vivantes GmbH, Berlin
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Franziska Szelinski
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Tuan Anh Le
- Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Andreia Lino
- Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
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Annika Glenzer
- Charité – Universitätsmedizin Berlin, Rheumatologie und Klinische Immunologie, Berlin; Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), ein Institut der Leibniz-Gemeinschaft, Berlin
| Veröffentlicht: | 30. August 2023 |
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Gliederung
Text
Introduction: The Antiphospholipid Syndrome (APS) is an autoimmune disorder, characterized by arterial-, venous- or small vessel thrombosis or miscarriages in the presence of anti-phospholipid autoantibodies (aPL). Despite these autoantibodies, B cells remain poorly studied in APS [1]. Besides tiple-positivity of aPL or the presence of lupus anticoagulant, there are no biomarkers for risk assessment in APS [2].
Methods: In this study, we analyzed PBMCs from 18 healthy controls (HC), 19 primary APS (pAPS) and 18 secondary APS (sAPS) patients. Using multi-dimensional flow cytometry, we studied the expression of 15 different surface markers, to characterize the B cell subset distribution in APS, with a focus on B cells reactive against Phosphatidylcholine (PtC). We developed a novel assay to detect B lineage cells directed against PtC as a potential correlate of aPL as reported previously for B1 cells in mice [3]. The obtained cellular subsets were subjected to the FlowSOM algorithm to identify B cell clusters in an unbiased manner.
Results: Frequencies of atypical CD21low and CD11c+ B cells are increased in pAPS and sAPS patients (pAPS and sAPS: p<0.05), which are described to be characteristic for autoimmune conditions.4,5 pAPS, but not sAPS patients, show significantly increased frequencies of total PtC-reactive B cells (p<0.05). In HCs, PtC-reactive B cells were mainly naïve, while they were significantly enriched in the IgD+CD27+ preswitch compartment in pAPS patients (p<0.01). Unsupervised clustering identified 8 distinct B cell clusters. Remarkably, PtC-reactive B cells mainly resided in clusters of atypical CD21lowCD11c+ memory B cells. When investigating anti-Phosphatidylcholine antibodies (aPtC) as a potential serological correlate of PtC-reactive B cells, we found increased serum levels of IgM (pAPS and sAPS: p<0.05) and IgG (pAPS: p<0.01, sAPS: p<0.0001) aPtC in APS patients compared to HCs.
Conclusion: Although APS patients show an overall comparable B cell subset distribution compared to HCs, atypical memory B cells are a characteristic of pAPS and sAPS patients. PtC-reactive B cells are present in HCs and APS patients, while they are substantially enriched in atypical memory compartments in APS. The data indicate that there is an ongoing induction of atypical autoantigen-specific memory B cells.
Figure 1 [Fig. 1]
References
- 1.
- Dieudonné Y, Guffroy A, Poindron V, Sprauel PS, Martin T, Korganow AS, Gies V. B cells in primary antiphospholipid syndrome: Review and remaining challenges. Autoimmun Rev. 2021 May;20(5):102798. DOI: 10.1016/j.autrev.2021.102798
- 2.
- Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, Cuadrado MJ, Dörner T, Ferrer-Oliveras R, Hambly K, Khamashta MA, King J, Marchiori F, Meroni PL, Mosca M, Pengo V, Raio L, Ruiz-Irastorza G, Shoenfeld Y, Stojanovich L, Svenungsson E, Wahl D, Tincani A, Ward MM. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019 Oct;78(10):1296-304. DOI: 10.1136/annrheumdis-2019-215213
- 3.
- Lino AC, Dang VD, Lampropoulou V, Welle A, Joedicke J, Pohar J, Simon Q, Thalmensi J, Baures A, Flühler V, Sakwa I, Stervbo U, Ries S, Jouneau L, Boudinot P, Tsubata T, Adachi T, Hutloff A, Dörner T, Zimber-Strobl U, de Vos AF, Dahlke K, Loh G, Korniotis S, Goosmann C, Weill JC, Reynaud CA, Kaufmann SHE, Walter J, Fillatreau S. LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells. Immunity. 2018 Jul 17;49(1):120-133.e9. DOI: 10.1016/j.immuni.2018.06.007
- 4.
- Glauzy S, Boccitto M, Bannock JM, Delmotte FR, Saadoun D, Cacoub P, Ice JA, Sivils KL, James JA, Wolin SL, Meffre E. Accumulation of Antigen-Driven Lymphoproliferations in Complement Receptor 2/CD21-/low B Cells From Patients With Sjögren's Syndrome. Arthritis Rheumatol. 2018 Feb;70(2):298-307. DOI: 10.1002/art.40352
- 5.
- Wang S, Wang J, Kumar V, Karnell JL, Naiman B, Gross PS, Rahman S, Zerrouki K, Hanna R, Morehouse C, Holoweckyj N, Liu H; Autoimmunity Molecular Medicine Team; Manna Z, Goldbach-Mansky R, Hasni S, Siegel R, Sanjuan M, Streicher K, Cancro MP, Kolbeck R, Ettinger R. IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE. Nat Commun. 2018 May 1;9(1):1758. DOI: 10.1038/s41467-018-03750-7
