How Co-Stimulatory/Inhibitory Molecules Vary Across Immune Cell Subtypes in the Severity of Systemic Lupus...

Co-stimulatory and co-inhibitory molecules are critical to T cell responses and involved in the pathogenesis of systemic lupus erythematosus (SLE). This study aimed to comprehensively analyze the surface expression of these molecules in various phenotypic immune cells, comparing the differences between various levels of the severity in SLE and control groups.

Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-Paque from blood samples of severe SLE patients (treatment with immunosuppressants), mild SLE patients (excluding those with persistent proteinuria or thrombocytopenia), and healthy controls (n = 10 each). PBMCs were stimulated for 48 h. The cells were stained with anti-CD3, CD4, CD28, PD-1, and CTLA-4 antibodies and analyzed by flow cytometry. Differences between groups were assessed using the Kruskal-Wallis test and Mann-Whitney U-test, with median values and statistical significance (p < 0.05) reported.

The results showed that CD28 expression was significantly higher in SLE patients compared to controls, with the highest levels in mild SLE. However, CD3⁺ CD28⁺ and CD4⁺ CD28⁺ cells were more prevalent in controls (p = 0.032 and 0.017, respectively). Mild SLE patients exhibited the highest CTLA-4 expression, with significant differences from severe SLE and controls (p = 0.030 and 0.037, respectively). PD-1 expression was lowest in severe SLE but highest in mild SLE within CD3⁺ CD4⁺ cells (p = 0.001). After 48 h of activation, CD4⁺ CTLA4⁺ and CD3⁺ CTLA4⁺ expression levels were significantly higher in controls compared to SLE groups.

Our study highlighted that the expression of CD28, CTLA-4, and PD-1 in lymphocytes and specific T cell subsets was various according the severity of SLE in patients, underscoring their roles in disease pathogenesis.