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蛋白酪氨酸磷酸酶非受体型22(PTPN22)1858C→T多态性、人类白细胞抗原-DRB1共享表位及自身抗体与类风湿关节炎的关联

Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis.

作者信息

Raslan Hala M, Attia Hanaa R, Salama Iman, Ibrahim Mona Hamed, Hassan Eman Mahmoud, El Hussieny Mohamed S, El Menyawi Manal M, Amr Khalda S

机构信息

Internal Medicine Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.

Clinical and Chemical Pathology Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.

出版信息

Rheumatol Int. 2016 Aug;36(8):1167-75. doi: 10.1007/s00296-016-3511-6. Epub 2016 Jun 20.

Abstract

To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5-3.5) and bone erosion (OR = 2.9, 95 % CI 1.1-7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9-204.4 for RA and OR = 69.4, 95 % CI 15.8-305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.

摘要

评估蛋白酪氨酸磷酸酶非受体型22(PTPN22)1858C→T多态性、人类白细胞抗原(HLA)共享表位及自身抗体对类风湿关节炎(RA)易感性和严重程度的影响。本研究共纳入150例RA患者和150例对照。采用酶联免疫吸附测定法(ELISA)检测抗环瓜氨酸肽抗体(抗CCP)及类风湿因子各亚型(IgG、IgM和IgA)。采用限制性片段长度多态性分析(RFLP)检测PTPN22 1858C→T多态性,采用聚合酶链反应-序列特异性引物分析(PCR-SSP)进行HLA-DRB1基因分型。对所有RA患者进行双手和双足的前后位单视角X线片检查。结果显示,PTPN22 1858 T等位基因与RA(比值比[OR]=2.3,95%可信区间[CI] 1.5 - 3.5)及骨侵蚀(OR=2.9,95% CI 1.1 - 7.6)相关。随着自身抗体阳性、HLA-DRB1共享表位与PTPN22 1858 T等位基因携带情况的组合,相关性增加。与抗CCP抗体组合时相关性最高(RA的OR=47.3,95% CI 10.9 - 204.4;侵蚀的OR=69.4,95% CI 15.8 - 305.5,P<0.001)。PTPN22 1858 T等位基因携带与类风湿因子阴性亚型或无HLA-DRB1共享表位的组合与RA无显著相关性。PTPN22 1858C→T多态性与HLA共享表位及自身抗体的存在增加了RA发生和侵蚀性疾病的风险。

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