Research ArticleAUTOIMMUNITY

Dynamics of the human antibody repertoire after B cell depletion in systemic sclerosis

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Science Immunology  29 Sep 2017:
Vol. 2, Issue 15, eaan8289
DOI: 10.1126/sciimmunol.aan8289

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A revealing repertoire for systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease associated with fibrosis and serious complications, including pulmonary arterial hypertension (PAH). Abnormal B cell responses have been associated with SSc pathogenesis, and de Bourcy et al. analyzed immunoglobulin heavy chain (IGH) transcripts of SSc-PAH patients enrolled in a B cell depletion clinical study. SSc-PAH was associated with several B cell development anomalies, particularly underuse of the IGHV2-5 segment and B cell homeostasis abnormalities. Depletion temporarily reversed these anomalous SSc-PAH disease signatures, and the data suggest that the rate of naïve B cell replenishment could be estimated from baseline measurements. These results define antibody signatures associated with SSc-PAH and reveal how B cell depletion shapes the antibody repertoire during reconstitution.