Effect of leflunomide on the superflcial costimulatory molecules spectrum of peripheral blood T lymphocytes in patients with lupus nephritis / 中华风湿病学杂志

ABSTRACT

Objective To investigate the effect of leflunomide on the superficial costimulatory molecules expression of T lymphocytes in patients with lupus nephritis ( LN ). Methods The peripheral blood mononuclear cells (PBMCs) of female active LN patients and healthy female were separated by density gradient centrifugation, and cultured by phytohemagglutinin (PHA) or leflunomide active metabolites(A771726).The CD28, CD40L, CTLA-4 and LFA-1a expressions on the peripheral blood T lymphocytes were detected by double-colored flow cytometry. The differences of the means were tested by analysis of variance( ANOVA ) and SNK q test. Results Comparing with healthy controls, there were significantly higher expressions of CD28,CD40L, LFA-1a and CTLA-4 on the peripheral blood T cells in active LN patients (CD2833.4±6.5 vs14.4±3.2; CD40L 13.2±3.2 vs 5.4±2.3; LFA-1a 8.5±2.3 vs2.2±1.1; CTLA-44.6±1.5 all P＜0.01) as well as CD28 and CD40L expression on the peripheral blood T cells from healthy controls induced by PHA (CD2826.8±6.7 vs14.4±3.2; CD40L 13.9±4.9 vs 5.4±2.3 all P＜0.01 ), but not CTLA-4 and LFA-1a expression.However, CD28, CD40L, LFA-1a and CTLA-4 expressions on T cells stimulated by PHA increased in active LN patients(all P＜0.05 ). A771726 could significantly inhibit over-expression of LFA-1a and CD40L on the T cells from active LN patients (CD40L8.2±2.0 vs13.3±3.2;LFA-1a5.1±1.3 vs8.5±2.3 all P＜0.01 ), but not CD28 and CTLA-4 expression. A771726 did not inhibit CD28, CD40L, LFA-1a and CTLA-4 expression on the T cells in healthy controls. Furthermore, A771726 could markedly inhibit the over-expression of all of the above molecules induced by PHA on the T cells of active LN patients (all P＜0.05). Conclusion One of the major mechanisms for LEF treatment of LN is that LEF can down-regulate CD40L and LFA-1a expression but not CD28 and CTLA-4 expression on the peripheral blood T cells in active LN patients.