Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene
Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene
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DOI：
10.1136/ard.2004.029447
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发表时间：
2005-07-01
影响因子：
27.4
通讯作者：
Shinar, Y
中科院分区：
文献类型：
--
作者：
Rabinovich, E;Livneh, A;Shinar, Y
背景：Pyrin 是一种新认识的细胞内炎症调节因子，编码 Pyrin 的基因 MEFV 的突变是家族性地中海热的原因。目的：确定 MEFV 的已知突变是否与类风湿性关节炎 (RA) 发病相关或可以改变 RA 的严重程度。方法：在 98 名以色列患有风湿性关节炎的患者中测定了三种最常见的 MEFV 突变：M694V、V726A 和 E148Q 的频率。 RA（74 名女性，24 名男性）并与 100 名来源匹配的健康受试者进行比较。 RA 严重程度是使用 126 级的新临床评分来确定的。通过逻辑回归消除混杂测量后，比较突变携带者和非携带者组的中位严重程度评分。结果：17/98 (17%) RA 患者（均为女性）为常见 MEFV 突变杂合，主要为 E148Q（12 名患者），1 名患者为 V726A 突变纯合。 RA 患者和健康受试者的总体突变率相当。携带突变的患者的中位严重程度评分高于非携带者组（42 vs 29，p = 0.0005）。在调整性别、类风湿因子的存在、发病年龄和病程后，逻辑回归模型将携带者中严重 RA 的比值比指定为 15 倍（n = 97，p = 0.01，95% CI 1.74 至 128）。结论：MEFV，尤其是 E148Q 突变，是 RA 临床表现的独立修饰因子。这是第二种 MEFV 突变已被证明会加重临床状况的 Th1 型自身免疫性疾病。
Background: Pyrin is a newly recognised intracellular regulator of inflammation, and mutations in MEFV, the gene encoding pyrin, are the cause of familial Mediterranean fever.Objective: To determine if known mutations of MEFV are associated with rheumatoid arthritis ( RA) morbidity or can modify RA severity.Methods: The frequency of the three most common MEFV mutations: M694V, V726A, and E148Q, was determined in 98 Israeli patients with RA ( 74 women, 24 men) and compared with that in 100 healthy subjects matched for origin. RA severity was determined using a new clinical score of 126 grades. The median severity score of mutation carrier and non-carrier groups was compared after confounding measures were eliminated by logistic regression.Results: 17/98 (17%) patients with RA ( all women) were heterozygous for common MEFV mutations, predominantly E148Q ( 12 patients), and one patient was homozygous for the V726A mutation. The overall mutation rate was comparable between patients with RA and healthy subjects. Patients carrying a mutation had a higher median severity score than the non-carrier group ( 42 v 29, p = 0.0005). The logistic regression model assigned a 15-fold odds ratio for severe RA in carriers, after adjusting for sex, presence of rheumatoid factor, age at onset, and disease duration ( n = 97, p = 0.01, 95% CI 1.74 to 128).Conclusion: MEFV, and particularly the E148Q mutation, is an independent modifier of the clinical manifestations of RA. This is the second Th1-type autoimmune disease in which MEFV mutations have been shown to aggravate the clinical status.