HLA-DRB1*0405影响MPO-ANCA相关性肾小球肾炎发生和预后的机制研究

抗中性粒细胞胞浆抗体（ANCA）相关性小血管炎（AASV）仍是临床和实验研究的热点，我国AASV患者以髓过氧化物酶（MPO）-ANCA最为多见，高达85%。研究表明，MHCII类分子参与了AASV的发生，我们的前期研究表明HLA-DRB1*0405参与了我国MPO-ANCA的发生并影响了疾病的预后。本研究进一步从功能方面进行探讨，利用患者的外周血白细胞分析HLA-DRB1*0405通过中性粒细胞递呈MPO多肽片段参与MPO-ANCA相关性肾小球肾炎的发生。对比研究HLA-DRB1*0405纯合子和非DRB1*0405携带MPO-ANCA患者，利用患者的血、尿和组织学标本，分别从基因和蛋白水平进行研究，阐明DRB1*0405通过TNF-α影响疾病预后的具体机制，并为治疗开辟新的途径。

Anti-neutrophil cytoplasmic antibodies （ANCA） associated systemic vasculitis （AASV） remains a subject of great experimental and clinical interest. Among chinese AASV patients，85% were Myeloperoxidase (MPO)-ANCA positive. Tremendous evidences have shown that MHC class II molecules involve in the pathogenisis of AASV. Our previous genetic study demonstrated that HLA-DRB1*0405 predisposed to develop MPO-ANCA disease and predicted the outcome of the disease. The study herein were designed using the neutrophils of patients to clarify whether DRB1*0405 be shown to be functionally involved in antigen presentation of MPO peptides stimulating MPO-ANCA associated glomerulonephritis formation. Another aim was to investigate whether DRB1*0405 affected the outcome of MPO-ANCA disease through TNF-αby comparing the levels of TNF-αprotein and/or mRNA in the serum, urine and kidney tissue of DRB1*0405 homozygous and non-DRB1*0405 MPO-ANCA patients. Thus, the potential benefits of inhibiting TNF-αin treating human MPO-ANCA disease will be suggested.