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46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

19.09. - 22.09.2018, Mannheim

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Belimumab treatment reduces B cell hyperactivity and type-I interferon expression in patients with systemic lupus erythematosus

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  • Jonas Martin - Charité – Universitätsmedizin Berlin, Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Deutsches Rheuma-Forschungszentrum Berlin, Leibniz Institut, Berlin
  • Qingyu Cheng - Charité – Universitätsmedizin Berlin, Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Deutsches Rheuma-Forschungszentrum Berlin, Leibniz Institut, Berlin
  • Sarah Laurent - Ludwig-Maximilians-Universität München, Institut für Klinische Neuroimmunologie, München
  • Franziska Thaler - Ludwig-Maximilians-Universität München, Institut für Klinische Neuroimmunologie, München
  • Edgar Meinl - Ludwig-Maximilians-Universität München, Institut für Klinische Neuroimmunologie, München
  • Andreas Radbruch - Deutsches Rheuma-Forschungszentrum (DRFZ), Berlin
  • Falk Hiepe - Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 46. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 32. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), Wissenschaftliche Herbsttagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Mannheim, 19.-22.09.2018. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocER.14

doi: 10.3205/18dgrh093, urn:nbn:de:0183-18dgrh0932

Published: February 5, 2019

© 2019 Martin et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Background: Belimumab is a monoclonal antibody against BAFF/BLyS and has been approved for patients with active systemic lupus erythematosus (SLE) despite standard of care immunosuppressive treatment (ST). Nevertheless, the interference of belimumab with pathogenetic pathways of SLE is not fully understood. B cell hyperactivity and overexpression of type-I interferons (IFN) have been shown to be key elements in the pathogenesis of SLE. This study demonstrates the effect of belimumab on biomarkers representing B cell hyperactivity and IFN expression in SLE patients.

Methods: 26 SLE patients treated with belimumab (BT), 82 SLE patients with ST and 30 matched healthy controls (HC) were recruited for this study. Siglec-1 expression on monocytes representing IFN signature, BCMA expression on different B cell subsets and the frequency of activated naive B cells (aNB) in PBMCs were analyzed by FACS. Serum levels of BAFF plus two of its soluble receptors sBCMA and sTACI were determined by ELISA.

Results: In comparison to ST, BCMA expression was reduced in BT on naive B cells (P<0.001) and memory B cells (P<0.05) but not on aNB, plasmablasts and plasma cells. In comparison to HC, BCMA expression was similar on all B cell subsets, except on aNB where it was higher in BT (P<0.001). The frequency of aNB among total B cells was reduced in BT compared to ST (P<0.001) and was comparable to HC. Siglec-1 expression on monocytes decreased after BT (P<0.05); ST and BT showed a rise compared to HC (each P<0.001).

Furthermore, serum BAFF levels in ST and BT were higher than in HC (each P<0.001), but did not differ significantly between BT and ST. Serum levels of sBCMA (P<0.05) and sTACI (P<0.001) were lower in BT compared to ST and also after belimumab treatment (each P<0.05). Besides, levels of sTACI in BT were even lower than in HC (P=0.01).

Conclusion: This study provides deeper insights into the impact of belimumab on several pathogenetic pathways of SLE activity. Regarding the inhibition of B cell hyperactivity and the reduction of IFN overexpression, two major pathogenetic elements of SLE, belimumab treatment showed distinct advantages by leading to a decline of them.