系统性红斑狼疮患者Clq受体和Clq抗体的表达及其与发病相关性的研究

The role of Clq receptor and anti-Clq antibody in the pathogenesis of systemic lupus erythematosus

目的检测系统性红斑狼疮(SLE)患者外周血单个核细胞ClqRp和gClqR的表达及与Clq抗体、补体Clq水平的关系,并进一步探讨其在SLE发病中的意义。方法用流式细胞计数法测定58例SLE和30名正常人外周血中性粒细胞、单核细胞、淋巴细胞的ClqRp和gClqR的表达,同时测血清Clq抗体、Clq水平,并将其与C3、C4、抗核抗体(ANA)、抗dsDNA抗体、SLEDAI积分做相关性分析。结果SLE患者外周血中性粒细胞、单核细胞的ClqRp表达为(7.2±2.3)%和(3.4±2.1)%,均较正常人[(10.6±2.1)%和(9.0±8.7)%]降低(P<0.05),淋巴细胞不表达ClqRp,但可表达gClqR。ClqRp在SLE活动期表达略低于稳定期,但差异无统计学意义。SLE患者的gClqR表达略高于正常人,gClqR在活动期高于稳定期,但差异无统计学意义。SLE患者血清Clq抗体水平(98±41)U/ml,明显高于正常,Clq为(0.13±0.08)g/L,低于正常值。外周血单个核细胞的ClqRp表达与血清ClqAb水平(Pearson m-0.574,P<0.05)、双链DNA(ds-DNA)抗体滴度呈负相关,与补体Clq(Peaton r=0.673,P<0.01)、C3、C4水平呈正相关。gClqR与Clq Ab和补体Clq无明显相关性。结论SLE患者外周血中性粒细胞、单个核细胞ClqR的表达缺陷,导致SLE吞噬功能受损,凋亡细胞清除障碍,诱导产生自身抗体,在SLE的免疫发病机制中起重要的作用。

Objective To investigate the expression of Clq complement receptor （C1qRp and gC1qR） in the peripheral blood mononuclear cells （PBMC） of systemic lupus erythematosus （SLE）, and the correlation between serum levels of complement 1q （C1q） and anti-C1q autoantibodies （C1qAb） with C1qRp and gC1qR is analyzed. The probable mechanism of C1qRp and gC1qR in the development of SLE is explored. Methods The peripherial blood monouclear cells of 58 SLE patients and 30 healthy subjects were collected for the detection of the expression of C1qRp and gC1qR by flow cytometry. The serum levels of C1q and C1qAh were detected by single radial immunodiffusion and enzyme-linked immunosorhent assay （ELISA） respectively. The correlation between C1qRp and gC1qR and other disease activity parameters, such as C1q, ClqAh, SLEDAI score, anti-dsDNA antibody, C3, C4 levels were analyzed. Results The expression of ClqRp on mononuclear and neutrophiles of SLE was （7.2±2.3）% and （3.4±2.1）%, lower than that in healthy individuals [ （ 10.6±2.1 ） % and （9.0±8.7） % ], P〈0.05 ）. The lymphocyte surface expression of C 1 qRp couldn＇t be detected. The percentage of cells positive for ClqRp was relatively higher in with PBMC from patients with active disease than with stable disease, there was no statistical significant difference. Meanwhile, gC1qR was detected in mononuclear and neutrophiles, as well as lymphocytes. The presentation of gC1q in PBMC was different from healthy controls, but there was no statistical significance. The serum level of anti-C1q autoantibodies in SLE patients was （98±41） U/ml, which was significanly increased. On the contrary, the level of Clq was much lower than that in healthy controls [（0.13±0.08） g/L]. The correlation coefficient between ClqR and ClqAb was -0.574 （P〈0.05）, showing a significant negative correlation. The correlation coefficient between C1qR and Clq was 0.673 （P〈0.01）, showing a significant positive correlation. The decrease of ClqRp was positively correlated with the decrease of C3, C4 and negatively with the level of dsDNA autoantibodies. The expression of gC1qR was less significantly correlated with the level of Clq, C1qAb, and disease activity parameters. Conclusion C1qRp and gClqR may be involved in the pathogenesis of SLE. The defective expression of ClqR do exist in SLE. Our results support the hypothesis that the lack of expression of ClqR may decrease the clearance of apoptotic cells and apoptotic bodies, which is uptaked by macrophage in a C1q-dependent pattern.