Abstract
Background SLE is an autoimmune disorder characterised by polyclonal Bcell activation, the production of anti-double stranded (ds) DNA autoantibodies and cytokines. Molecular and clinical studies regarding SLE often address clinically active patientsand 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 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 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 analysed.
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.
