engleski

Immunomodulatory therapy, B cells and autoimmune disease

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems, and is characterized by presence of various autoantibodies. As production of some autoantibodies correlates with tissue pathology (i.e. anti-dsDNA antibodies and glomerulonephritis), B cells are thought to play a role in SLE pathogenesis. Indeed, numerous abnormalities in B cell activation, signaling, cytokine production and selection were observed in SLE patients. Studies on certain mouse models of SLE discovered that Toll-like receptor 9 (TLR9) activation in autoreactive B cells by DNA-IgG immune complexes triggered the disease development. However, human studies often included patients on different immunomodulatory therapy. Therefore we aimed to examine whether and how the drugs commonly used in SLE treatment affect B cells. We measured B cell activation and B-cell activating factor receptor (BAFF-R) expression in in vitro cultures of human peripheral blood mononuclear cells (PBMC) activated by CpG (a synthetic TLR9 ligand) and co-cultured with chloroquine and/or dexamethasone. Moreover, we examined whether glucocorticoid and chloroquine treatment influence TLR9 expression in B cells and serum BAFF levels in 11 newly-diagnosed SLE patients before therapy, after initial three-week glucocorticoid course, and again after three months when chloroquine was introduced into the protocol. Modulation of TLR9 expression detected in patients undergoing therapy was also confirmed in in vitro conditions. Since in SLE patients we found no correlation between measured parameters and disease activity (expressed as SLEDAI score), it is likely that the observed differences in TLR9 expression and BAFF levels before and during treatment result from the drugs themselves, and do not reflect clinical features of the disease.

B cells; TLR9; Toll-like receptors; autoimmunity; systemic lupus erythematosus; chloroquine; corticosteroids

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