Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (rs=0.283, P=0.049) and serum albumin (rs=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; rs=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE.

T细胞免疫球蛋白黏蛋白结构域（T-cell immunoglobulin and mucin domain, TIM）家族与自身免疫性疾病相关，但目前尚不明确其在系统性红斑狼疮（systemic lupus erythematosus, SLE）患者免疫细胞中的表达水平。本研究旨在探讨TIM-3 mRNA的表达是否与SLE的发病机制相关。本研究采用实时定量逆转录聚合酶链反应（quantitative real-time reverse transcription-polymerase chain reaction, qRT-PCR），检测132例SLE患者与62例健康对照者外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）中TIM-1、TIM-3及TIM-4 mRNA的表达水平；同时采用流式细胞术，检测20例SLE患者及15例健康对照者PBMC表面TIM家族蛋白的表达水平。结果显示，与健康对照者相比，SLE患者的TIM-3 mRNA表达水平显著降低（P<0.001），而SLE患者与健康对照者白细胞的TIM家族蛋白表达水平无显著差异（P>0.05）。伴狼疮肾炎（lupus nephritis, LN）的SLE患者TIM-3 mRNA表达水平显著低于不伴LN的SLE患者（P=0.001），但不同病理类型LN患者的TIM-3 mRNA表达水平无显著差异（P>0.05）。TIM-3 mRNA表达水平与血清IgA水平呈显著正相关（r=0.425, P=0.004），与血清总蛋白（rs=0.283, P=0.049）及血清白蛋白（rs=0.297, P=0.047）呈弱相关；与系统性红斑狼疮疾病活动指数（Systemic Lupus Erythematosus Disease Activity Index, SLEDAI）呈弱负相关（rs=-0.272, P=0.032）。本研究结果提示，PBMC中TIM-3 mRNA表达低于正常水平可能参与SLE的发病机制。