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意大利北部与风湿性多肌痛相关的HLA - DRB1等位基因:与疾病严重程度的相关性

HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity.

作者信息

Salvarani C, Boiardi L, Mantovani V, Ranzi A, Cantini F, Olivieri I, Bragliani M, Collina E, Macchioni P

机构信息

Servizio di Reumatologia, Arcispedale S Maria Nuova, Reggio Emilia, Italy.

出版信息

Ann Rheum Dis. 1999 May;58(5):303-8. doi: 10.1136/ard.58.5.303.

Abstract

OBJECTIVE

To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.

METHODS

A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation.

RESULTS

No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7).

CONCLUSION

These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.

摘要

目的

在一个地中海国家研究人类白细胞抗原-DRB1(HLA-DRB1)等位基因与风湿性多肌痛(PMR)的关联,并探讨HLA-DRB1基因在决定疾病严重程度中的作用。

方法

对意大利雷焦艾米利亚风湿病二级转诊中心连续诊断的92例PMR患者进行了为期五年的前瞻性随访研究。通过聚合酶链反应扩增和寡核苷酸杂交,在92例患者、29例DR4阳性类风湿关节炎(RA)患者和来自同一地理区域的148例对照中确定HLA-DRB1等位基因。

结果

在PMR患者和对照之间,HLA-DRB1类型的频率以及HLA-DRB 70-74共有基序的表达未观察到显著差异。双剂量表位患者的频率较低,在PMR患者和对照中无显著差异。在DR4+ PMR、DR+ RA和DR4+对照之间,未观察到HLA-DR4亚型分布的显著差异。单因素分析结果表明,诊断时红细胞沉降率(ESR)>72 mm/第1小时、HLA-DR1、DR10、类风湿表位的存在以及类风湿表位的类型是与复发/再发相关的显著危险因素。Cox比例风险模型确定了两个独立增加复发/再发风险的变量:诊断时ESR>72 mm/第1小时(RR=1.5)和2型(由非DR4等位基因编码)类风湿表位(RR=2.7)。

结论

来自一个地中海国家的数据显示,在意大利北部患者中,类风湿表位与PMR无关联。诊断时高ESR以及由非DR4等位基因编码的类风湿表位的存在是疾病严重程度的独立有价值标志物。

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