类风湿关节炎患者抗环瓜氨酸肽抗体与人类白细胞抗原-DR4等位基因相关性研究

The study on anti-cyclic citrullinated peptide antibody associated with HLA-DR4 alleles expression in patients with rheumatoid arthritis

目的研究类风湿关节炎（RA）及未分类关节炎（痛）（UA）患者抗环瓜氨酸肽（CCP）抗体与人类白细胞抗原（HLA）-DR4等位基囚相关性。方法对91例RA患者，46例UA患者，35名健康志愿者，均为浙江汉族人，应用酶联免疫吸附试验（ELISA）法检测血清抗CCP抗体，序列特异性引物聚合酶链反应（PCR—SSP）检测HLA—DR4等位基因。结果RA组、UA组HLA—DR4阳性率分别为47．2％、45．6％，均以DRB1＊0405为主，分别为25．3％、23．9％。RA组、UA组患者的抗CCP抗体与HLA—DR4具有相关性（r=0．613，0．703，P〈0．01），与HLA—DRB1＊0405具有弱相关性（r=0．304，P〈0．01；r=0．333，P〈0．05）。2组HLA—DR4阳性患者抗CCP抗体水平明显高于HLA—DR4阴性患者，差异有统计学意义（P〈0．01）。抗CCP抗体、HLA—DR4均阳性患者红细胞沉降率（ESR）、C反应蛋白（CRP）、血小板水平明显升高，晨僵时间延长，关节肿胀度积分升高，与二者阴性患者比较，差异有统计学意义（P〈0．05或P〈0．01）。对UA组患者3个月后随访，抗CCP抗体、HLA—DR4在早期RA的阳性率为94．7％（18／19）。结论抗CCP抗体与HLA—DR4、DRB1＊0405相关；抗CCP抗体、HLA—DR4均阳性反映了RA病情活动性；联合检测抗CCP抗体、HLA—DR4或DRB1＊0405有助于RA早期诊断；抗CCP抗体可能在HLA—DR4等遗传因素参与下介导了RA发病。

Objective To explore the association between anti-cyclic citrullinated peptide （ACCP） antibody with HLA-DR4 alleles expression in patients with rheumatoid arthritis （RA） and unclassified arthritis[arthralgia] （UA）. Methods ACCP antibody was detected by ELISA and HLA-DR4 alleles by PCR- SSP in 91 RA patients, 46 UA patients and 35 healthy controls. All subjects of this study were Zhejiang Han people. Results The positive rate of HLA-DR4 and DRB1 ＊ 0405 in patients with RA and UA was 47.2%, 25.3; 45.6%, 23.9% respectively. ACCP antibody in patients with RA and UA was associated with HLA-DR4 （r=0.613, 0.703; P〈0.01 ）, and it was weakly associated with HLA-DR4 allele DRB1＊0405 （r=0.304, P〈 0.01; r=0.333, P〈0.05）. ACCP antibody in patients with positive HLA-DR4 was significantly higher than those with negative HLA-DR4 （P〈0.01）. Levels of ESR, CRP, PLT, score of joint swelling, the duration of morning stiffness in patients with positive ACCP antibody and HLA-DR4 was significantly higher than those in patients with negative HLA-DR4 （P〈0.05, or P〈0.01 ）. In 19 out of 46 patients with UA were early RA after 3 months follow up. 94.7% （18/19） UA patients with positive ACCP antibody and HLA-DR4 were early RA. Conclusion ACCP antibody is associated with HLA-DR4 and DRB1 ＊ 0405. RA and UA patients with positive ACCP antibody and HLA-DR4 reflects disease activity. Combining ACCP antibody and HLA-DR4 or DRB1 ＊ 0405 is helpful in the diagnosis of early RA. ACCP antibody plays an important role in the pathogenesis of RA by cooperating with HLA-DR4 precipitation.