Morel P A, Chang H J, Wilson J W, Conte C, Saidman S L, Bray J D, Tweardy D J, Medsger T A
Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, PA.
Hum Immunol. 1994 Jun;40(2):101-10. doi: 10.1016/0198-8859(94)90054-x.
SSc is an autoimmune connective tissue disease in which strong HLA associations have not been described. Anti-topo I antibodies are recognized, in general, in SSc patients with diffuse cutaneous involvement, whereas anti-ACAs are found in individuals with limited cutaneous involvement. We studied 95 Caucasian SSc patients, 44 with anti-topo I antibodies and 51 with neither anti-topo I nor ACA, for HLA-DR associations by using DNA typing techniques. We analyzed 181 normal Caucasian individuals in the same fashion. A significant association was observed in the anti-topo-I-positive patients with DRw11 (p = 1.7 x 10(-6), RR 4.2). The distribution of DRw11 alleles in these patients was significantly different from that observed in controls and could be accounted for by an increase in the frequency of the DRB1*1104 allele (p = 1.2 x 10(-9), RR 9.5). The DRw11 alleles were also associated with SSc with more tendon friction rubs (p = 0.006), which is a marker of more severe disease. In addition, a strong association was observed with anti-topo I antibodies and a particular sequence (aa 71-77) of the DQB1 chain (p = 0.02, RR 2.2). HLA associations in the case of SSc patients with anti-topo I antibodies are complex and involve at least two genes: HLA-DRw11, which appears to play a major role in determining the severity of the disease, and a DQ sequence, which associates with the development of the anti-topo I antibodies.
系统性硬化症（SSc）是一种自身免疫性结缔组织疾病，目前尚未发现其与HLA有很强的关联性。一般来说，抗拓扑异构酶I抗体在弥漫性皮肤受累的SSc患者中被识别出来，而抗着丝点抗体（ACAs）则在局限性皮肤受累的个体中被发现。我们采用DNA分型技术，研究了95例白种人SSc患者，其中44例有抗拓扑异构酶I抗体，51例既无抗拓扑异构酶I抗体也无抗着丝点抗体，以确定其与HLA - DR的关联性。我们以同样的方式分析了181例正常白种人个体。在抗拓扑异构酶I阳性患者中观察到与DRw11有显著关联（p = 1.7 x 10(-6)，相对危险度RR = 4.2）。这些患者中DRw11等位基因的分布与对照组观察到的分布显著不同，这可能是由于DRB1*1104等位基因频率的增加所致（p = 1.2 x 10(-9)，RR = 9.5）。DRw11等位基因还与有更多肌腱摩擦音的SSc相关（p = 0.006），这是疾病更严重的一个标志。此外，还观察到抗拓扑异构酶I抗体与DQB1链的一个特定序列（氨基酸71 - 77）有很强的关联（p = 0.02，RR = 2.2）。对于有抗拓扑异构酶I抗体的SSc患者，HLA的关联性很复杂，至少涉及两个基因：HLA - DRw11，它似乎在决定疾病严重程度方面起主要作用；以及一个DQ序列，它与抗拓扑异构酶I抗体的产生相关。
