gms | German Medical Science

45. Kongress der Deutschen Gesellschaft für Rheumatologie, 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

06.09. - 09.09.2017, Stuttgart

Characterization of SLE B cells from patients in remission – persistent IL-10 secretory defect

Meeting Abstract

  • Magdalena Siekierka-Harreis - Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität, Rheumatologie, Düsseldorf
  • Madita Schroedter - Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität, Rheumatologie, Düsseldorf
  • Ralph Brinks - Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
  • Birgit Opgenoorth - Poliklinik und Funktionsbereich für Rheumatologie & Hiller Forschungszentrum Rheumatologie Universitätsklinikum der Heinrich-Heine-Universität Düsseldorf, Rheumatologie, Düsseldorf
  • Jutta Richter - Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
  • Stefan Vordenbäumen - Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
  • Matthias Schneider - Poliklinik, Funktionsbereich & Hiller Forschungszentrum für Rheumatologie, UKD, Heinrich-Heine-Universität Düsseldorf, Düsseldorf
  • Georg Pongratz - Universitätsklinik Düsseldorf, Poliklinik, Funktionsbereich und Hiller Forschungszentrum Rheumatologie, Düsseldorf

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Stuttgart, 06.-09.09.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocER.03

doi: 10.3205/17dgrh078, urn:nbn:de:0183-17dgrh0783

Published: September 4, 2017

© 2017 Siekierka-Harreis 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

Text

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by polyclonal B cell activation and by the production of anti-double stranded (ds) DNA autoantibodies (aabs) and cytokines. Even in a clinical quiescent state subclinical inflammation causes further damage. Molecular and clinical studies regarding SLE often address clinically active patients and not patients in remission. This study reports on immunoglobulin, anti-dsDNA-aab and IL-10 secretory capacity of cultures of CD19+ lymphocytes from SLE patients in remission in comparison to normal donors. The aim was to evaluate whether endogenous factors (BAFF, CD40, IL4), exogenous factors (CpG-ODN-motifs, SAC) or their combinations differentially influence immunoglobulin, cytokine and anti-dsDNA-aab production in not active SLE patients vs. healthy controls.

Methods: Blood samples were obtained from a group of 13 SLE patients attending clinics at the rheumatology unit at the Heinrich-Heine University hospital in Düsseldorf and from 5 healthy controls (HC). All patients fulfilled the revised criteria of the American College of Rheumatology for SLE and were randomly collected in clinical remission state (SLEDAI 1,1 ± 1,8). The medication consisted of prednisolone (5/13 patients), mycophenolate mofetil (3/13 patients), azathioprine (1/13 patients), hydroxychloroquine (8/13 patients) or was without immunosuppression.

After 6 days of cell culture in the absence or presence of the aforementioned stimuli, levels of IgG, IgM, dsDNA antibodies and interleukin-10 (IL-10) were determined in the supernatants by ELISA. The effect of the stimuli alone or in combination on IgG, IgM, anti-dsDNA-aab, and IL-10 production was analyzed by two different statistical models.

Results: Peripheral B cells from SLE patients in remission or control subjects did not show any difference in IgG, IgM, and anti-dsDNA-aabs to all aforementioned stimuli. The addition of CpG and SAC to cell cultures showed a stimulatory effect on immunoglobulin, cytokine and anti-dsDNA-aab production in SLE B cells and healthy controls alike. The amount of anti-dsDNA IgG-type autoantibodies produced by peripheral B cells was negligible. However, B cells from SLE patients showed diminished capacity to produce IL-10 as compared to B cells from healthy donors (SLE Estimate -40.17, Std.error 17.21, p <0.01).

Conclusion: B cells from SLE patients in remission as compared to peripheral B cells from healthy donors have comparable capacity to secrete immunoglobulin including non-IgG anti-dsDNA-aabs whereas their capacity to secrete IL-10 is impaired. This suggests a persisting intrinsic defect of B regulatory cells in SLE.