少儿强直性脊柱炎与幼儿类风湿性关节炎HLA-B27亚型的鉴别诊断(英文)

Differential diagnosis of juvenile ankylosing spondylitis and juvenile rheumatoid arthritis by subtypes of HLA-B27 alleles

背景:少儿强直性脊柱炎( juvenile ankylosing spondylitis, JAS)和幼儿类风湿关节炎( juvenile rheumatoid arthritis, JRA)与 HLA-B27抗原关联研究已近 25年历史,国外有学者报道强直性脊柱炎( ankylosing spondylitis, AS)和关节炎与 HLA-B27等位基因亚型关联不同. 目的:探讨 HLA-B27等位基因亚型与 JAS和 JRA的关联性及其在发病机制中的作用 ,以期能够找到早期诊断 JAS检测方法. 设计:非随机对照的实验研究. 地点、对象和方法:纳入 60 例北京儿童医院住院及门诊的 JAS和 JRA患者, 5个家系中患者的父亲或母亲 5例及 9例正常个体(来源于 200多例健康自愿骨髓移植供者).用 PCR/SSP方法对 74例 HLA-B27等位基因亚型进行研究 ,并进行关联分析. 主要观察指标: JAS和 JRA与 HLA-B27等位基因亚型相关性分析; HLA-B* 2704等位基因在 JAS和 JRA中的差异 ;家系资料 ;单倍型分析 ;纯合子分析.表明 HLA-B* 2704与 C* 1202连锁紧密而与 HLA-A连锁不紧密, JAS有明显家族遗传倾向. 结果: 本组人群的 HLA-B27等位基因由 HLA-B* 2704,* 2705,* 2702,* 2707 4种亚型组成 ,其中 JAS患者 HLA-B27等位基因亚型频率 B* 2704为 56.25% ;B* 2705为 40.63% ;B* 2702为 3.13% ;JRA HLA-B27等位基因亚型频率为 B* 2705为 60.7% ;B* 2704为 28.57%; B* 2702为 3.57% 及 B* 2707为 7.14% ;JAS与 JRA结果比较 , HLA-B* 2704基因频率在 JAS组高于 JRA组 (RR=3.21,P< 0.05). 结论:JAS与 HLA-B* 2704等位基因亚型关联.对 HLA-B27等位基因亚型的检测 ,可成为 JAS和 JRA鉴别诊断中一个有价值实验指标.

BACKGROUND:The relationship of juvenile ankylosing spondylitis(JAS) and juvenile rheumatoid arthritis(JRA) with HLA-B27 alleles has been studied for about 25 years.Some researchers abroad reported that the relationship between ankylosing spondylitis and HLA-B27 allele subtypes is different from that between arthritis and HLA-B27 allele subtypes.OBJECTIVE:To investigate the relationship of JAS and JRA with HLA-B27 allele subtypes and its role in the pathogenesis so as to find out the testing methods for earlier diagnosis of JAS or JRA.DESIGN:Non-random control laboratory study. SETTING,PARTICIPANTS and INTERVENTIONS:A total of 60 patients diagnosed with JAS or JRA in Beijing Children's Hospital were recruited,including 5 fathers or mothers from 5 patients' families,compared with 9 normal controls (from 200 donors for bone marrow transplantation).We studied 74 cases of HLA-B27 allele subtypes and analyzed their correlation by using PCR/SSP. MAIN OUTCOME MEASURES:Correlation of JAS and JRA with HLA-B27 allele subtypes;difference of HLA-B 2704 between JAS and JRA;data of patients' families.Haplotypes analysis and homozygote analysis on patients' families showed that there existed a close link between HLA-B' 2704 and C 1202,but not with HLA-A,and that JAS had a remarkable tendency of family inheritance. RESULTS:HLA-B 2704,2705,2702 and 2707 were found in the cases.In JAS group,allelic frequency of HLA-B27 was B 2704 56.25%,B 2705 40.63% and B 2702 3.13%,respectively.However,in JRA group,it was B 2705 60.7%,B 2704 28.57%,B 2702 3.57% and B 2707 7.14%,respectively.Comparison between JAS and JRA showed that the allelic frequency of HLA-B 2704 in JAS patients was higher than that in JAS patients(RR = 3.21,P < 0.05). CONCLUSION:The susceptibility of JAS is positively associated with subtypes HLA-B 2704.Testing HLA-B27 subtypes may be a valuable marker in differential diagnosis of JAS and JRA.