Session Type: Abstract Submissions (ACR)
CD22 is a negative co-receptor of the B-cell receptor (BCR) and, when targeted by epratuzumab, partially inhibits BCR signaling, for example by reducing Syk phosphorylation and Ca2+ flux. Cytokines produced by B cells have been described as playing important roles during certain stages of autoimmune diseases such as systemic lupus erythematosus (SLE) and their secretion is known to be driven by antigens and/or Toll-like receptor (TLR)-ligand stimulation. However, the impact of epratuzumab, a monoclonal antibody that targets CD22, on cytokine production has not yet been addressed. The current study therefore aimed to analyze the role of epratuzumab on the production of key cytokines by B cells, and compare the response of B cells from SLE patients to those from healthy donors (HD).
Peripheral blood mononuclear cells were isolated and B cells purified by Magnetic Activated Cell Sorting®. After 2 days of culture in the presence of TLR9 and/or BCR stimulation (CpG and anti-IgM/IgG, respectively), cytokine production (IL-6, TNF-α and IL-10) by B cells from SLE patients and HD was analyzed in the supernatants by bioplex. A special focus was made on IL-10-producing B cells using intracellular staining by flow cytometry. The balance between IL-10 and pro-inflammatory cytokines were assessed using the ratios of the concentrations of IL-10 to either IL-6 or TNF-α.
The secretion of the pro-inflammatory cytokines TNF-α and IL-6 by anti-BCR activated HD and SLE B cells was significantly inhibited by epratuzumab co-treatment. The production of both cytokines was also inhibited by epratuzumab when B cells were stimulated concomitantly through the BCR and TLR9, although this failed to reach statistical significance for IL-6 production from HD. In contrast, the production of IL-10 in B cell supernatants was not affected by epratuzumab under any stimulation conditions; similarly, the development of IL10+ cells in culture, which was enhanced by TLR and BCR activation, was unaffected by epratuzumab. The cytokine balance between IL-10 and pro-inflammatory cytokines was influenced toward the regulatory cytokine IL-10.
Epratuzumab, through the targeting of CD22, inhibited the production of the pro-inflammatory cytokines IL-6 and TNF-α by B cells after stimulation through BCR and TLRs pathways, but had no effect on IL-10. This suggests that this antibody has the capacity to regulate the balance between the regulatory cytokine IL-10 and pro-inflammatory cytokines, and suggests a potential mechanism of action of epratuzumab on the effector function of B cells.
S. J. Fleischer,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/targeting-cd22-with-epratuzumab-impacts-cytokine-production-by-b-cells/