Research ArticleAutoimmunity

Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis

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Science Translational Medicine  20 Nov 2019:
Vol. 11, Issue 519, eaaw4626
DOI: 10.1126/scitranslmed.aaw4626

When B cells are bad to the bone

B cells may contribute to rheumatoid arthritis pathogenesis through additional mechanisms beyond autoantibodies. Mensah et al. observed that a subset of patients with rheumatoid arthritis had defective ataxia telangiectasia–mutated (ATM) expression, which among other pathways controls gene rearrangements in B cells. This group of patients had a skewed B cell repertoire and erosive bone lesions. In vitro experiments revealed that ATM-deficient B cells expressed factors that would promote bone resorption. An ATM inhibitor in humanized mice recapitulated the B cell defects and bone erosion observed in patients. These results identify a pathogenic B cell axis in rheumatoid arthritis that could potentially be targeted with B cell–depleting therapies.

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