Lymphocyte subset clustering analysis in treatment-naive patients with systemic lupus erythematosus

The aim of the study is to identify clusters of lymphocyte subsets within treatment-naive systemic lupus erythematosus (SLE) patients and evaluate the potential association of these clusters with disease activities.

We conducted a cross-sectional study of consecutive 143 treatment-naive SLE patients in the Affiliated Hospital of Nantong University, China. We used hierarchical cluster analysis to classify individuals into clusters based on circulating lymphocyte subset proportions (CD3⁺CD4⁺T cell, CD3⁺CD8⁺T cell, CD19⁺B cell, and CD3-CD16 + CD56 NK cell) via R software. Demographic variables, clinical manifestations, laboratory variables, and disease activities were compared among clusters.

The SLE patients (median age 35 (26-48) years, 90.9% female) were divided into four clusters. The clustering features were as follows: cluster 1 (B high), cluster 2 (CD4 high), cluster 3 (CD8 high), and cluster 4 (NK high). SLE patients in cluster 1 showed the highest incidence of arthritis (70.6%, 34.2%, 48.3%, and 42.9% in clusters 1, 2, 3, and 4, respectively; P = 0.046), and patients in cluster 3 and cluster 4 showed significantly a higher incidence of nephritis (35.3%, 25.0%, 48.3%, and 61.9% in in clusters 1, 2, 3, and 4, respectively; P = 0.008). Patients in cluster 2 suffered from lower SLE Disease Activity Index (SLEDAI) score (12.1 ± 5.0, 10.3 ± 5.6, 12.2 ± 4.6, and 14.4 ± 7.3 in clusters 1, 2, 3, and 4, respectively; P = 0.046). Regression analysis indicated that, compared with patients in cluster 2, patients in cluster 1 exhibited higher rate of arthritis (OR 4.53, 95% CI 1.38-14.86, P = 0.013), while patients in cluster 3 (OR 2.85, 95%CI 1.15-7.08, P = 0.024) and cluster 4 (OR 4.93, 95%CI 1.76-13.85, P = 0.002) exhibited higher rate of nephritis.

This study supports the existence of lymphocyte subset clusters with different clinical features in treatment-naive SLE patients, which could help to differentiate between various subsets of SLE. Key Points • Lymphocyte subsets may occur in a pattern of cluster in treatment-naive SLE patients.