Aetiopathogenesis
Regulatory B cell imbalance correlates with Tfh expansion in systemic sclerosis
L. Ricard1, F. Malard2, S. Riviere3, C. Laurent4, O. Fain5, M. Mohty6, B. Gaugler7, A. Mekinian8
- INSERM U938, Centre de Recherche Saint-Antoine, Paris, and Sorbonne Université, Paris, France.
- INSERM U938, Centre de Recherche Saint-Antoine, Paris, Sorbonne Université, Paris, and Service d'Hématologie Clinique, AP-HP, Hôpital Saint-Antoine, Paris, France.
- Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), AP-HP, Hôpital Saint-Antoine, Paris, France.
- INSERM U938, Centre de Recherche Saint-Antoine, Paris, and Sorbonne Université, Paris, France.
- INSERM U938, Centre de Recherche Saint-Antoine, Paris, and Sorbonne Université, Paris, France.
- INSERM U938, Centre de Recherche Saint-Antoine, Paris, Sorbonne Université, Paris, and Service d'Hématologie Clinique, AP-HP, Hôpital Saint-Antoine, Paris, France.
- INSERM U938, Centre de Recherche Saint-Antoine, Paris, France.
- INSERM U938, Centre de Recherche Saint-Antoine, Paris; Sorbonne Université, Paris, and Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), AP-HP, Hôpital Saint-Antoine, Paris, France. arsene.mekinian@aphp.fr
CER14270
2021 Vol.39, N°4 ,Suppl.131
PI 0020, PF 0024
Aetiopathogenesis
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PMID: 34323682 [PubMed]
Received: 26/11/2020
Accepted : 19/02/2021
In Press: 28/07/2021
Published: 28/07/2021
Abstract
OBJECTIVES:
Systemic sclerosis (SSc) is an autoimmune disease with fibrosis, microangiopathy and immune dysfunction. B cell abnormalities characterised 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 analyse the frequency of regulatory B (Breg) cell subsets and the correlation with Tfh in SSc patients.
METHODS:
Circulating Breg cells CD24hiCD38hi and CD27+CD24hi levels and cTfh cells CD4+CXCR5+PD1+ were determined by cytometry in 50 SSc patients and 32 healthy subjects.
RESULTS:
The frequency of Breg cells CD24hiCD38hi and CD24hiCD27+ was significantly reduced in patients with SSc as compared to controls (p=0.02 and p<0.001, respectively). In contrast, when examining the CD21low B cell subset, the frequency was significantly increased in SSc patients compared to healthy controls, (p<0.001). There was no difference in Breg cell levels in patients with diffuse SSc and limited SSc. However, CD24hiCD27+ 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 CD24hiCD27+ 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 CD24hiCD27+ Breg cell frequency may contribute to the development of SSc.