Peripheral blood lymphocyte subsets and heterogeneity of B cell subsets in patients of idiopathic inflammatory myositis with different myositis-specific autoantibodies

Abstract

Abstract Objective To explore the characteristics and clinical significance of lymphocyte subsets, especially B cell subsets in patients with idiopathic inflammatory myositis (IIM). Methods A total of 176 patients with IIM in active disease condition and 210 gender/age-matched healthy controls (HCs) were included in our study. Demographic characteristics and lymphocyte subset patterns were compared between the two groups. In addition, B cell subsets from 153 patients with IIM and 92 HCs were characterized. Based on principal component analysis (PCA) of B cell subsets, patients with IIM were classified into three different subgroups by hierarchical cluster analysis. Subsequently, demographic characteristics, antibody types and clinical characteristics were compared among the subgroups. Results Patients with IIM have reduced counts of peripheral lymphocyte subsets compared with HCs, which included T cells, B cells, and natural killer cells. Also, B cell subsets were altered in patients with IIM. The percentages of memory B cells and translational memory B cells were reduced, while CD19 + B cells, plasmablast and naïve B cells were increased. Moreover, to explore the heterogeneity of B cells in IIM patients, patients were categorized into 3 clusters based on B cell subset clustering analysis. Cluster 1 was dominated by CD19 + B cells, Bregs and Naïve B cells, cluster 3 was dominated by Memory B cells and plasmablast, and the proportion of B cell subsets in cluster 2 was in between. Notably, the patients of cluster 1 had the highest proportion of anti-TIF1-γ antibodies, whereas cluster 3 showed an elevated proportion of anti-MDA5 + antibodies. Chest tightness was more prominent in clusters 2 and 3 compared to clusters 1. Moreover, B cell subsets were correlated with multiple laboratory parameters. Conclusion Our study indicated that lymphopenia is a common manifestation in patients with IIM. B cell subsets are abnormally expressed and showed high heterogeneity in patients with IIM by cluster analysis. The clinical characteristics and laboratory parameters differed among the three clusters.