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