This review aims to summarize current evidence for a role of B-cells in the pathogenesis of systemic sclerosis (SSc) from genetics to phenotypes, with an emphasis on recent insights.
Multiple genomic analyses have associated several B-cell signalling genes with SSc. Moreover, interesting B-cell subset alterations and activation/memory marker changes have also been documented in SSc. Co-cultures of blood B-cells with dermal fibroblasts isolated from SSc patients demonstrated the induction of collagen, interleukin (IL)-6, transforming growth factor (TGF)-β1, IL-1β and chemokine (c-c motif) ligand 2 (CCL2) in the fibroblasts, following potential B-cell cues delivered to the fibroblasts. Plasma cell gene signatures were elevated in SSc patients’ blood, and highly correlated with collagen gene expression. Finally, anti-CD20 B-cell depletion therapy not only improved skin disease but also preserved interstitial lung disease in early diffuse cutaneous disease.
Thus, there is resounding evidence that B-cells play a pivotal role in pathogenesis of SSc. However, the molecular pathways through which B-cells may direct fibroblast function, SSc disease development and progression remain unclear, and warrant further study.
aDivision of Rheumatology & Clinical Immunogenetics, The University of Texas Health Science Center at Houston
bDepartment of Biomedical Engineering, University of Houston, Houston, Texas, USA
*Both Minghua Wu and Chandra Mohan contributed equally to this work.
Correspondence to Dr Chandra Mohan, Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Houston, TX-77004 USA. Tel: +1 713 743 3709; fax: +1 713 743 0226; e- mail: firstname.lastname@example.org