Increased CD21-CD27- atypical memory B cells as a biomarker of clinical disease activity in patients with systemic lupus erythematosus

Abstract Background Determining disease activity in systemic lupus erythematosus (SLE) patients is challenging and limited by the lack of reliable biomarkers. Analysis of the altered distribution of circulating B cells has shown promise for assessment disease activity. Yet studies are limited by variable classifications of B subsets. Therefore, we studied peripheral B cells using high-dimensional tools to identify a valid biomarker of disease activity.Methods We studied B cells in two separate cohorts of patients included in the Swiss SLE Cohort Study. In discovery cohort A, we analyzed cryopreserved PBMCs from 30 SLE, and 30 age-, sex- and ethnicity matched healthy controls (HC) by mass cytometry. In validation cohort B, fresh blood from 63 SLE, 14 Sjögren syndrome (pSS), 14 Sarcoidosis (Sarc), and 39 age-matched HC were analyzed by flow cytometry.Results In cohort A, using unsupervised clustering analysis, we identified 7 metaclusters within B cells. Two metaclusters were increased in SLE and exhibited a phenotype of atypical memory B cells (aMBC): CD21-, CD27-, CD11c+ and CXCR5-. Based on cohort A results, we confirmed in cohort B the increase in CD21-CD27- aMBC in SLE, compared to healthy and disease controls. In both cohorts, aMBC were associated with the severity of clinical manifestations. Compared to classical biomarkers, aMBC showed a significant correlation with clinical signs of disease activity. Conclusion aMBC were expanded in SLE, and the increase correlated with clinical disease activity. According to our data, aMBC represents a robust and easily accessible biomarker to assess disease activity in patients with SLE.