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Deprecated: Implicit conversion from float 280.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Arthritis+Res+Ther 2015 ; 17 (1): ä Nephropedia Template TP
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Epratuzumab inhibits the production of the proinflammatory cytokines IL-6 and TNF-?, but not the regulatory cytokine IL-10, by B cells from healthy donors and SLE patients #MMPMID26183319
Arthritis Res Ther 2015[]; 17 (1): ä PMID26183319show ga
Introduction: Cytokines produced by B cells are believed to play important roles in autoimmune diseases. CD22 targeting by epratuzumab has been demonstrated to inhibit phosphorylation of B cell receptor (BCR) downstream signaling in B cells. It has been shown that other sialoadhesin molecules related to CD22 have immunoregulatory functions; therefore, in the present study, we addressed the role of epratuzumab on the production of key cytokines by B cells of patients with systemic lupus erythematosus (SLE) and of healthy donors (HD). Methods: Peripheral blood B cells were purified and activated by BCR with or without Toll-like receptor 9 (TLR9) stimulation in the presence or absence of epratuzumab. Cytokine production by B cells (interleukin [IL]-6, tumor necrosis factor [TNF]-? and IL-10) in the supernatant and the induction of IL-10+ B cells from patients with SLE and HD were analyzed. Results: The secretion of the proinflammatory cytokines TNF-? and IL-6 by anti-BCR and BCR- and/or TLR9-activated B cells from HD and patients with SLE was inhibited by epratuzumab. In contrast, the production of IL-10 by B cells was not affected by epratuzumab under either stimulation condition. Consistently, the induction of IL-10?producing B cells in culture was not affected by epratuzumab. Conclusions: Epratuzumab, by targeting CD22, was able to inhibit the production of the proinflammatory cytokines IL-6 and TNF-? by B cells, in contrast to IL-10, in vitro. These data suggest that targeting CD22 alters the balance between proinflammatory cytokines (TNF-?, IL-6) and the regulatory cytokine IL-10 as another B cell effector mechanism.