Level of CD4 + central memory T cells and its clinical correlation in childhood-onset systemic lupus erythematosus

Abstract

Objectives

This study aims to investigate CD4⁺ central memory T cells (CD4⁺ TCM) levels in childhood-onset systemic lupus erythematosus (cSLE) and their association with disease activity, clinical features, and treatment responses.

Methods

A total of 202 children with newly diagnosed, untreated rheumatic diseases were recruited, comprising 64 cases of cSLE, 71 cases of juvenile idiopathic arthritis, 31 cases of juvenile dermatomyositis, 36 cases of autoinflammatory diseases, and 22 healthy controls. Lymphocyte subsets were analyzed using multi-color flow cytometry, and clinical data and laboratory test results were collected. The correlation between CD4⁺ TCM levels and SLEDAI scores, clinical manifestations, autoantibodies, and kidney injury markers was examined. Subsequently, 21 cSLE patients underwent follow-up assessments and retesting post-treatment.

Results

The proportion of CD4⁺ TCM (44.3 ± 11.5%) in cSLE was significantly higher compared to those with other pediatric rheumatic diseases (p < .05). A negative correlation was observed between the level of CD4⁺ TCM and the SLEDAI-2000 score (r = −0.255, p = .021), indicating that higher disease activity was associated with lower CD4⁺ TCM levels. Furthermore, CD4⁺ TCM levels were negatively correlated with oral ulcers (r = −0.285, p = .011) and positively correlated with leukopenia (r = 0.302, p = .008). In terms of laboratory indicators, CD4⁺ TCM showed negative correlations with anti-dsDNA antibodies (r = −0.294, p = .009) and anti-histone antibodies (r = −0.232, p = .033), while exhibiting a positive correlation with anti-Sm antibodies (r = 0.245, p = .025). Additionally, CD4⁺ TCM demonstrated significant negative correlations with early renal injury markers, urinary transferrin (r = −0.315, p = .008), and urinary microalbumin (r = −0.284, p = .015). CD4⁺ TCM was strongly negatively correlated with CD4⁺ Naive cells (r = −0.831, p < .001), positively correlated with other memory cell subsets, and negatively correlated with IFN-α levels (r = −0.364, p = .031). Longitudinal analysis revealed a time-dependent biphasic pattern in CD4⁺ TCM levels. Cyclophosphamide-treated patients showed significantly increased CD4⁺ TCM levels compared to non-cyclophosphamide groups (p = .034).

Conclusions

CD4⁺ TCM likely plays a central immune regulatory role in cSLE, with its levels closely associated with disease activity, specific autoantibody production, and early organ damage. Post-treatment changes in CD4⁺ TCM levels may indicate therapeutic efficacy and suggest their potential as biomarkers, offering a fresh perspective on immune memory regulation in cSLE and exploring novel treatment approaches.