Systemic Lupus Erythematosus (SLE) is characterized by a prominent increase in expression of type-I interferon (IFN)-regulated genes in 50-75% of patients. Here we investigate the presence of autoantibodies (auto-Abs) against type I IFN in SLE patients and their possible role in controlling disease severity. We report that out of 491 SLE patients, 66 had detectable anti-IFNα-auto-Abs. The presence of neutralizing anti-IFNα- auto-Abs correlates with lower levels of circulating IFNα protein, inhibition of IFN down- stream signalling molecules and gene signatures and with an inactive global disease
score. Previously reported B cell frequency abnormalities, found to be involved in SLE pathogenesis, including increased levels of immature, double negative and plasmablast B cell populations were partially normalized in patients with neutralising anti-IFNα-auto- Abs compared to other patient groups. We also show that sera from SLE patients with neutralising anti-IFNα-auto-Abs biases in vitro B cell differentiation towards classical memory phenotype, while sera from patients without anti-IFNα-Abs drives plasmablasts differentiation. Our findings support a role for neutralising anti-IFNα-auto-Abs in controlling SLE pathogenesis and highlight their potential efficacy as novel therapy.
Regulatory B cells (Bregs) have regulatory capacity via the production of IL-10. IL-10 expression and immunosuppression has been described in a number of human B cell subsets, two of which include the CD19 + CD24 hi CD38 hi and CD19 + CD24 hi CD27 + populations. In this chapter, we describe how to identify and isolate these subsets from peripheral blood B cells via flow cytometry. We also explain how to expand Bregs in culture and identify them based on intracellular expression of IL-10.
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