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Pathogenic antibodies

Nature 574, 122–126 (2019)

Pathogenic autoantibodies contribute to various immune-mediated diseases. Whether distinct immune-mediated diseases in humans share similar features that shape their circulating B cell pool and hence their B cell antigen receptor (BCR) repertoires has remained unknown. In Nature, Smith and colleagues report a comparative analysis of circulating BCR repertoires from newly diagnosed patients across six distinct autoimmune diseases. Among the parameters analyzed are frequency of the gene cluster encoding the immunoglobulin heavy-chain variable region, and its isotype and diversity, as well as clonal size and inferred relationships between naive B cells and antigen-experienced B cells. The BCR repertoires of patients with systemic lupus erythematosus exhibit the expected differences relative to those of healthy control subjects but, surprisingly, so do the BCR repertoires of patients with Crohn’s disease or eosinophilic granulomatosis, despite the fact that these diseases have not been associated with pathogenic B cells previously. The authors find increased circulating titers of immunoglobulin A (IgA) or IgE or both IgA and IgE in all three diseases. Importantly, they note differences in patient responses to anti–B cell therapies. These features can provide insights into strategies for treating patients with these diseases.

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Correspondence to Laurie A. Dempsey.

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Dempsey, L.A. Pathogenic antibodies. Nat Immunol 20, 1414 (2019).

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