Class IIHLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP
Class IIHLA associations with autoantibodies in scleroderma: a highly significant role for HLA-DP
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DOI：
10.1038/sj.gene.6363734
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发表时间：
2001-04-01
影响因子：
5
通讯作者：
du Bois, RM
中科院分区：
文献类型：
--
作者：
Gilchrist, FC;Bunn, C;du Bois, RM
硬皮病是一种表型可变的病症，其特征是皮肤和内脏器官纤维化。在患者血清中发现了一系列疾病特异性自身抗体。本研究的目的是：（1）研究MHC，特别是HLA-DP在自身抗体产生中的作用； (2)调查与自身抗体的临床关联。我们使用 PCR 和序列特异性引物对 202 名硬皮病患者和 307 名英国对照受试者的 DNA 样本进行了 HLA II 类分型。所有患者都有明确的临床表型。检查患者血清中是否存在疾病特异性自身抗体，特别是抗拓扑异构酶自身抗体（ATA）、抗着丝粒自身抗体（ACA）和抗RNA聚合酶自身抗体（ARA）。 HLA-DPB1*1301 和 ATA 之间存在显着关联 (P-corr = 0.0001)。此外，ATA 与 HLA-DRB1*11 相关，抗着丝粒自身抗体 (ACA) 与 HLA-DRB1*04、HLA-DRB1*08 (P = 0.001) 以及第 26 位有甘氨酸残基的 HLA-DQB1 等位基因相关。在临床表型和自身抗体之间检测到非常强的关联。 ATA与肺纤维化相关（P = 0.00002），抗RNA聚合酶自身抗体（ARA）与肾脏受累（P = 0.0000006）和弥漫性皮肤病（P = 0.00001）相关，ACA与有限的皮肤受累（P = 0.00002）和预防肺纤维化相关（P = 0.0000003）。我们已经确定 ATA 和 HLA-DPB1*1301 之间存在显着关联，这可能有助于深入了解这种自身抗体的形成方式。患者的临床特征取决于他们携带的自身抗体。
Scleroderma is a condition of variable phenotype characterised by fibrosis of the skin and internal organs. There is a range of disease-specific autoantibodies found in the sera of patients. The aims of this study were to: (1) investigate the role of the MHC and particularly HLA-DP in the production of autoantibodies; (2) investigate clinical associations with autoantibodies. We have performed HLA class II typing using PCR with sequence-specific primers on DNA samples from 202 scleroderma patients and 307 UK control subjects. All patients had well defined clinical phenotypes. Sera from patients were examined for the presence of disease specific autoantibodies in particular the anti-topoisomerase autoantibody (ATA), the anti-centromere autoantibody (ACA) and the anti-RNA polymerase autoantibody (ARA). There was a striking association between HLA-DPB1*1301 and ATA (P-corr = 0.0001). In addition, ATA was associated with HLA- DRB1*11 and the anticentromere autoantibody (ACA) with HLA-DRB1*04, HLA-DRB1*08 (P = 0.001) and HLA-DQB1 alleles with a glycine residue at position 26. Very strong associations were detected between clinical phenotypes and autoantibodies. ATA was associated with pulmonary fibrosis (P = 0.00002), anti-RNA polymerase autoantibody (ARA) with renal involvement (P = 0.0000006) and diffuse skin disease (P = 0.00001), and ACA with limited skin involvement (P = 0.00002) and protection against pulmonary fibrosis (P = 0.0000003). We have identified a significant association between the ATA and HLA-DPB1*1301 which may provide an insight into how this autoantibody is formed. Patient clinical characteristics depend on the autoantibodies they carry.