Goronzy Jörg J, Matteson Eric L, Fulbright James W, Warrington Kenneth J, Chang-Miller April, Hunder Gene G, Mason Thomas G, Nelson Audrey M, Valente Robert M, Crowson Cynthia S, Erlich Henry A, Reynolds Rebecca L, Swee Ronald G, O'Fallon W Michael, Weyand Cornelia M
Mayo Clinic, Rochester, Minnesota 55905, USA.
Arthritis Rheum. 2004 Jan;50(1):43-54. doi: 10.1002/art.11445.
To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA).
The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+,CD28(null) T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs.
After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB104 alleles, particularly homozygosity for HLA-DRB104, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+,CD28(null) T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene.
Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.
确定可预测早期类风湿关节炎（RA）患者发生进行性侵蚀性疾病的预后标志物。
该研究纳入了111例疾病持续时间<1年的连续性RA患者起始队列。患者按照一种算法进行治疗，该算法旨在避免对轻症疾病过度治疗，并加速对具有持续疾病活动的患者的治疗。对患者进行临床和实验室疾病活动标志物检查。我们通过流式细胞术测定CD4 +、CD28（阴性）T细胞的频率，通过聚合酶链反应（PCR）/测序测定HLA - DRB1基因多态性，并通过多重PCR和与固定化探针阵列杂交测定19个候选基因中的26个单核苷酸多态性。使用比例优势模型分析数据，以确定在连续的手部/腕部X线片上预测2年内侵蚀进展的预后标志物。
2年后，队列中52%的患者疾病活动通过羟氯喹和非甾体类药物治疗得到控制。48%的患者未出现侵蚀。年龄较大、基线时存在侵蚀、存在类风湿因子、类风湿因子滴度以及HLA - DRB104等位基因，尤其是HLA - DRB104纯合子，是放射学进展的单因素预测指标。有前景的新标志物是作为免疫衰老指标的CD4 +、CD28（阴性）T细胞频率以及子宫珠蛋白基因的多态性。
早期RA患者的临床疾病活动通常可通过非激进治疗得到控制，但这并不总是足以预防新的侵蚀。类风湿因子滴度、HLA - DRB1多态性、年龄和免疫衰老标志物是放射学预后不良的预测指标。子宫珠蛋白基因的多态性可能识别出侵蚀性疾病风险较低的患者。
