GENETIC TYPING OF PATIENTS WITH INFLAMMATORY ARTHRITIS AT PRESENTATION CAN BE USED TO PREDICT OUTCOME
GENETIC TYPING OF PATIENTS WITH INFLAMMATORY ARTHRITIS AT PRESENTATION CAN BE USED TO PREDICT OUTCOME
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DOI：
10.1002/art.1780370809
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发表时间：
1994-08-01
影响因子：
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通讯作者：
EMERY, P
中科院分区：
文献类型：
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作者：
GOUGH, A;FAINT, J;EMERY, P
Objective.为了验证这一假设，即患者在出现炎性关节炎时的遗传特征可以预测随后的破坏性疾病。我们评估了177例早期关节炎患者。对患者进行类风湿因子（RF）的血清学检测，并对DRB 1基因第三高变区（HVR 3）中保守碱基序列的存在进行DNA寡聚型分析，该基因先前被证明与严重的类风湿关节炎（RA）相关。使用限制性片段长度多态性分析证实了患者基因型的纯合性。主要的结局指标是1年时的放射学侵蚀。120例患者符合美国风湿病学会1987年的RA诊断标准，其中64%的患者具有保守的碱基序列，而347例健康对照者为45%（P < 0.001），57例其他炎性关节炎患者为56%（P无显著性）。在RA人群中，Dw 4/Dw 14复合杂合子的频率不成比例地增加。HVR 3或RF的存在对糜烂的相对风险为13.49，敏感性为95%（特异性39%）; HVR 3和RF的存在的相对风险为8.13，特异性为88%（敏感性53%）。除1例Dw 4/Dw 14基因型患者外，其余患者均在1年内发生糜烂。患者的HLA-DR类型和RF状态的知识允许临床上有用的预测糜烂性疾病;具有Dw 4/Dw 14的患者代表特别高的风险亚组。
Objective. To test the hypothesis that genetic characterization of patients at the time they present with inflammatory arthritis can predict subsequent destructive disease.Methods. We evaluated 177 patients with early arthritis. Patients were serologically tested for rheumatoid factor (RF) and were DNA oligotyped for the presence of conserved base sequences in the third hypervariable region (HVR3) of the DRB1 gene, previously shown to be associated with severe rheumatoid arthritis (RA). Homozygosity in the patient's genotype was confirmed using restriction fragment length polymorphism analysis. The main outcome measure was radiologic erosions at 1 year.Results. At presentation, 120 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 64% of whom possessed the conserved base sequences, compared with 45% of 347 healthy controls (P < 0.001) and with 56% of 57 patients with other inflammatory arthritis (P not significant). Within the RA population, the frequency of Dw4/Dw14 compound heterozygotes was disproportionately increased. The presence of either HVR3 or RF had a relative risk of 13.49 for erosions, with a sensitivity of 95% (specificity 39%); the presence of both HVR3 and RF had a relative risk of 8.13, with a specificity of 88% (sensitivity 53%). All but 1 patient with the Dw4/Dw14 genotype developed erosions within 1 year.Conclusion. Knowledge of a patient's HLA-DR type and RF status allows clinically useful prediction of erosive disease; patients possessing Dw4/Dw14 represent a particularly high-risk subgroup.