Association of human leukocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis
Association of human leukocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis
复制标题
DOI：
10.2169/internalmedicine.38.336
复制
发表时间：
1999-04-01
影响因子：
1.2
通讯作者：
Mimori, T
中科院分区：
文献类型：
--
作者：
Kuwana, M;Inoko, H;Mimori, T
对象：为研究人类白细胞抗原（HLA）II类基因在系统性硬化症（SSc）发生发展中的作用以及在SSc患者临床和血清学表达中的作用，方法：通过基因分型确定HLA-DRB 1、DRB 3、DRB 4、DQB 1和DPB 1等位基因;通过间接免疫荧光、免疫双扩散和免疫沉淀鉴定血清抗核抗体。结果：DRB 1和DQB 1等位基因频率在SSc患者和健康对照组之间无显著性差异，而DPB 1 *0901在SSc患者中略有升高，而SSc相关自身抗体与SSc临床特征密切相关。HLA Ⅱ类基因检测结果：抗DNA拓扑异构酶I抗体与弥漫性皮肤受累、肺纤维化、DRB 1 *1502-DQB 1 *0601-DPB 1 *0901、抗U1 RNP抗体与狼疮和/或肌炎、DRB 1 *0401/*0802-DQB 1 *0302重叠;抗着丝点抗体与皮肤受累有限，DRB 1 *0101-DQB 1 *0501-DPB 1 *0402。在对SSc患者的HLA II类与临床特征的相关性分析中，仅获得了DRB 1 *0405患者与无DRB 1 *0405患者相比关节炎和类风湿因子频率增加的显著差异。HLA II类基因强烈影响SSc相关自身抗体的产生，而不是SSc的发展，此外，SSc是由血清自身抗体定义的独特亚群的复合疾病，其具有特异性临床和HLA II类相关性。
Object: To examine the role of human leukocyte antigen (HLA) class II genes in the development of systemic sclerosis (SSc) as well as in the clinical and serologic expression of SSc in patients,Methods: HLA-DRB1, DRB3, DRB4, DQB1, and DPB1 alleles were determined by genotyping; and serum antinuclear antibodies were identified using indirect immunofluorescence, double immunodiffusion and immunoprecipitation,Patients: One hundred and five Japanese patients with SSc and 104 race-matched healthy controls.Results: Frequencies of DRB1 and DQB1 alleles were not different between SSc patients and healthy controls, while DPB1*0901 was marginally increased in SSc patients, In contrast, SSc-related autoantibodies were closely associated with the clinical features. HLA class II genes were detected as follows: anti-DNA topoisomerase I antibody with diffuse cutaneous involvement, pulmonary fibrosis, and DRB1*1502-DQB1*0601-DPB1*0901; anti-U1RNP antibody with overlapping features of lupus and/or myositis and DRB1*0401/*0802-DQB1*0302; and anticentromere antibody with limited cutaneous involvement and DRB1*0101-DQB1*0501-DPB1*0402. In the analysis of the association of HLA class II and the clinical features in SSc patients significant differences were obtained only for the increased frequencies of arthritis and rheumatoid factor in patients with DRB1*0405 compared to those without.Conclusion: HLA class II genes strongly influence the production of SSc-related autoantibodies rather than the development of SSc, In addition, SSc is a composite disease of distinctive subsets defined by serum autoantibodies, which have specific clinical and HLA class II associations.