Article
Characterization of SLE B cells from patients in remission – persistent IL-10 secretory defect
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Published: | September 4, 2017 |
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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.