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Autoantibodies appear in the serum years before the development of clinical disease in patients ultimately diagnosed with systemic lupus erythematosus (SLE) or Sjögrens syndrome. The transition from benign to pathogenic autoimmunity is not understood. Anti-IgG rheumatoid factors provide an illuminating example of an autoantibody that persists, on average, more than four years prior to the development of systemic vasculitis and type II cryoglobuinemia. The aim of this study was to identify the pathogenic changes occurring in B cells making rheumatoid factor autoantibody during this transition.

Massively parallel sequencing of peripheral blood B cell receptors (BCR) was combined with mass spectrometry peptide sequencing of serum rheumatoid factor autoantibodies to identify circulating B cells expressing IgM rheumatoid factors in 4 patients with SLE or Sjögrens syndrome. In a patient …