THE INFLUENCE OF HLA-DRB1 GENES ON DISEASE SEVERITY IN RHEUMATOID-ARTHRITIS
THE INFLUENCE OF HLA-DRB1 GENES ON DISEASE SEVERITY IN RHEUMATOID-ARTHRITIS
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DOI：
10.7326/0003-4819-117-10-801
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发表时间：
1992-11-15
影响因子：
39.2
通讯作者：
GORONZY, JJ
中科院分区：
文献类型：
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作者：
WEYAND, CM;HICOK, KC;GORONZY, JJ
目的：探讨HLA-DRB 1基因在确定类风湿关节炎疾病严重程度中的作用。设计：血清阳性类风湿关节炎患者的病例系列。设置：马约诊所风湿科门诊。患者：102例血清阳性、糜烂性类风湿关节炎患者，最短病程为3年。测量：对患者进行两种HLA-DRB 1等位基因的基因分型，并根据一种或两种疾病相关的HLA-DRB 1等位基因的表达进行分类。通过聚合酶链反应和随后的寡核苷酸杂交进行HLA-DRB 1等位基因的鉴定。通过序列分析证实等位基因变体的纯合性。免疫遗传学定义的患者亚组进行了回顾性评价关节破坏和疾病表现的模式，包括类风湿性器官diseases.Results：102例患者中，98（96%）表达的疾病连锁序列多态性。47名患者（46%）携带双倍剂量的相关序列延伸：28名患者在两个等位基因上表达HLA-DRB 1 *04变体，19名患者将HLA-DRB*04变体与HLA-DRB 1 *0101或DRB 1 *1402结合。在HLA-DRB 1 *04/04型患者中，100%存在结节病，而在HLA-DRB 1 *04型患者中，59%仅遗传了单剂量疾病连锁序列多态性（P < 0.0001）。两组患者的主要器官系统受累率分别为61%和11%（P < 0.0001），关节手术率分别为61%和25%（P < 0.002）。HLA-DR*04/01分型的患者有中间临床courses.Conclusion：基因分型的类风湿关节炎患者HLA-DRB 1等位基因识别的疾病表现的不同配置文件的临床子集。
Objective: To explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis.Design: Case series of patients with seropositive rheumatoid arthritis.Setting: The outpatient clinic of the Division of Rheumatology, Mayo Clinic.Patients: One hundred and two patients with seropositive, erosive rheumatoid arthritis and a minimum disease duration of 3 years.Measurements: Patients were genotyped for both HLA-DRB1 alleles and were categorized according to the expression of one or two disease-linked HLA-DRB1 alleles. Identification of HLA-DRB1 alleles was done by the polymerase chain reaction and subsequent oligonucleotide hybridization. Homozygosity for allelic variants was confirmed by sequence analysis. Immunogenetically defined patient subgroups were retrospectively evaluated for joint destruction and patterns of disease manifestation, including rheumatoid organ disease.Results: Of 102 patients, 98 (96%) expressed the disease-linked sequence polymorphism. Forty-seven patients (46%) carried a double dose of the relevant sequence stretch: Twenty-eight patients expressed HLA-DRB1*04 variants on both alleles, and 19 combined an HLA-DRB*04 variant with HLA-DRB1*0101 or DRB1*1402. Nodular disease was present in 100% of patients typed as HLA-DRB1*04/04 and in 59% of patients typed as HLA-DRB1 *04 and who had inherited only a single dose of the disease-linked sequence polymorphism (P < 0.0001). Major organ systems were involved in 61% and 11% of these two patient groups, respectively (P < 0.0001); and joint surgery was required in 61% and 25% (P < 0.002), respectively. Patients typed as HLA-DR*04/01 had intermediate clinical courses.Conclusion: Genotyping patients with rheumatoid arthritis for both HLA-DRB1 alleles identifies clinical subsets with distinct profiles of disease manifestations.