Regulatory B Cell Imbalance Correlates With TFH Expansion in Systemic Sclerosis.

Objective: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis, microangiopathy and immune dysfunction. B cell abnormalities characterized by autoantibody production and polyclonal B cell activation play an important role in the pathogenesis of SSc. We previously identified an expansion of functional and activated circulating T follicular helper (cTfh) cells in SSc patients. The aim of this study was to analyze the frequency of regulatory B (Breg) cell subsets and the correlation with Tfh in SSc patients. Methods: . Circulating Breg cells CD24 h iCD38 hi and CD27 + CD24 hi levels and cTfh cells CD4 + CXCR5 + PD1 + were determined by cytometry in 50SSc patients and 32 healthy subjects. Results: . The frequency of Breg cells CD24 hi CD38 hi and CD24 hi CD27 + was significantly reduced in patients with SSc as compared to controls (p=0.02 and p<0.001, respectively). In contrast, when examining the CD21 low B cell subset, the frequency was significantly increased in SSc patients compared to healthy controls, (p<0.001). There was no difference in Bregcell levels in patients with diffuse SSc and limited SSc. However, CD24 hi CD27 + Breg cell frequency was significantly decreased in SSc patients with pulmonary arterial hypertension (p=0.014), but not in patients with interstitial lung disease (p=0.058).Furthermore, we observed a negative correlation between cTfh and CD24 hi CD27 + Breg cell levels in SSc patients but not in healthy controls (p=0.02). Conclusions: : These results suggest that Breg cell subsets may participate in the regulation of cTfh and disease severity. Decreased CD24 hi CD27 + Breg cell frequencymay contribute to the development of SSc.