TY - JOUR
T1 - B-cells in systemic sclerosis
T2 - Emerging evidence from genetics to phenotypes
AU - Wu, Minghua
AU - Mohan, Chandra
N1 - Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Purpose of review. 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. Recent findings. 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. Summary. 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.
AB - Purpose of review. 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. Recent findings. 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. Summary. 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.
KW - Antibodies
KW - Autoimmunity
KW - Cytokines
KW - Fibrosis
KW - Systemic sclerosis
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U2 - 10.1097/BOR.0000000000000215
DO - 10.1097/BOR.0000000000000215
M3 - Review article
C2 - 26285102
AN - SCOPUS:84942508804
SN - 1040-8711
VL - 27
SP - 537
EP - 541
JO - Current Opinion in Rheumatology
JF - Current Opinion in Rheumatology
IS - 6
ER -