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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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CD38 expression is up-regulated on memory B- and T-cell subsets in systemic lupus erythematosus (SLE)

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  • Lennard Ostendorf - Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Deutsches Rheumaforschungszentrum (DRFZ), Berlin
  • Falk Hiepe - Charité – Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin
  • Tobias Alexander - 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.22

doi: 10.3205/18dgrh101, urn:nbn:de:0183-18dgrh1011

Published: February 5, 2019

© 2019 Ostendorf 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: The resistance of long-lived plasma cells (PC) to immunosuppressive and B-cell depleting therapy constitutes a therapeutic challenge in antibody-mediated autoimmune diseases, such as systemic lupus erythematosus (SLE). Novel approaches targeting PC, e.g. anti-CD38 therapy, have therefore emerged. Here, we aimed to analyze expression levels of CD38 on plasmablast and lymphocyte subsets in SLE.

Methods: Multicolor FACS analysis was performed to investigate CD38-expression on peripheral blood CD19+ B-cell as well as CD4+ and CD8+ T-cell subsets from SLE patients (n=36, median SLEDAI 4, median age 40), compared to healthy donors (HD, n=20). Patients with multiple myeloma (MM, n=10) and Sjoegrens syndrome (SS, n=10) served as control.

Results: Circulating plasmablasts display the highest CD38-expression levels, but no significant differences were observed between patient groups. Among B-cells, only CD27+IgD+ unswitched memory B-cells in SLE had significantly higher CD38 mean fluorescence intensity (MFI) compared to HD (p<0.0005). In contrast, on CD4+ T-cells, CD38-expression in SLE was significantly higher in both CCR7+ CD45RA- TCM (median 28.3 vs. 40.8%, p<0.005) and CCR7- CD45RA- TEM (median 13.3 vs. 28.9%, p<0.001) subsets. Compared to their CD38- counterparts, CD38+ T-cell subsets had higher co-expression levels of HLA-DR and Ki-67. Although the frequency of Foxp3+Helios+ CD4+ Tregs was higher in SLE vs. HC (12.8 vs. 7.1%, p<0.001), the majority of CD38-expressing T-cells were confined to the Foxp3-Helios- conventional T cell subset. Similar to CD4+ T-cells, SLE CD8+ T-cells had significantly higher expression levels of CD38 on all memory subsets compared to HC, in particular TCM (p<0.0001), TEM (p=0.0001), and TE(p<0.0001).

Conclusion: Expression levels of CD38 are significantly higher in both, peripheral memory B- and T-cell subsets from patients with SLE compared to HD. CD38+ T-cells co-express markers of recent activation and proliferative history and are confined to conventional T-cells, reflecting a chronically activated memory T-cell compartment. Therapies targeting CD38, like Daratumumab, would therefore potential provide a therapeutic approach by targeting both long-lived PCs and their pre-activated precursor memory lymphocytes.