engleski

Conventional treatment modulates B cell TLR9 expresssion and IL-10 and BAFF production in systemic lupus erythematosus

Dual nature of B cells – armed with pattern-recognition receptors but capable for antigen-specific response – can become detrimental if an autoantigen elicits both pathways in self-sustained fashion. In systemic lupus erythematosus (SLE), a B cell-dependent autoimmune disease, such antigen is DNA. B cells recognize DNA via Toll-like receptor 9 (TLR9). Anti-DNA antibodies are prototypic for SLE, and antibody-complexed DNA stimulates self-reactive B cells in mice. B cell activation is also augmented by IL-10 (produced upon TLR9 signaling) and their survival maintained by BAFF (B-cell activating factor). Both cytokines are often found increased in SLE patients’ sera. Since some aspects of SLE are effectively controlled by chloroquine, a drug that inhibits TLR9 signaling, we investigated whether chloroquine modulates TLR9, IL-10 and BAFF levels in newly discovered SLE patients. TLR9 expression was measured in peripheral blood B cells by flow cytometry, and IL-10 and BAFF determined in sera by ELISA in 3 time-points: before treatment, after 3 weeks on corticosteroids, and after 3 months when chloroquine was introduced and steroids tapered. We also examined how chloroquine and steroids modulate TLR9 activation and B cell IL-10 production induced by synthetic CpG DNA, as well as BAFF levels and BAFF-receptor expression in cultures of isolated peripheral blood mononuclear cells. Samples for analysis were obtained both from patients and healthy controls. Measured parameters did not correlate with disease activity or autoantibody production. However, ex vivo and in vitro experiments suggest that immunomodulatory drugs substantially influence TLR9, IL-10 and BAFF levels. Therefore treatment is an important parameter to be considered when interpretating immunological studies in humans. Supported by Croatian MSES grant #021-1080229-0337 to A.G.

B cells; Toll-like receptors; TLR9; IL-10; BAFF; BLyS; systemic lupus erythematosus; autoimmunity; corticosteroids; chloroquine

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