SEVERE SYSTEMIC-SCLEROSIS WITH ANTI-TOPOISOMERASE-I ANTIBODIES IS ASSOCIATED WITH AN HLA-DRW11 ALLELE
SEVERE SYSTEMIC-SCLEROSIS WITH ANTI-TOPOISOMERASE-I ANTIBODIES IS ASSOCIATED WITH AN HLA-DRW11 ALLELE
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DOI：
10.1016/0198-8859(94)90054-x
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发表时间：
1994-06-01
期刊：
影响因子：
2.7
通讯作者：
MEDSGER, TA
中科院分区：
文献类型：
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作者：
MOREL, PA;CHANG, HJ;MEDSGER, TA
SSc是一种自身免疫性结缔组织疾病，其中强烈的HLA关联尚未被描述。一般而言，在弥漫性皮肤受累的SSc患者中识别抗拓扑I抗体，而在皮肤受累有限的个体中发现抗ACA抗体。我们研究了35例高加索SSc患者，44例抗拓扑蛋白I抗体和51例既没有抗拓扑蛋白I也没有ACA，HLA-DR协会通过使用DNA分型技术。我们以同样的方式分析了181名正常的高加索人。在抗topo-I阳性患者中观察到与DRw11显著相关（p = 1.7 × 10（-6），RR 4.2）。DRw11等位基因在这些患者中的分布与在对照组中观察到的显著不同，并且可以通过DRB 1 * 1104等位基因频率的增加来解释（p 1.2 X 10（-9），RR 9.5）。DRw11等位基因也与SSc相关，肌腱摩擦次数更多（p = 0.006），这是更严重疾病的标志。此外，观察到抗拓扑异构酶I抗体与DQB1链的特定序列（aa 71 - 77）的强关联（p = 0.02，RR 2.2）。在SSc患者的情况下，HLA与抗Topo I抗体的关联是复杂的，并且涉及至少两个基因：HLA-DRw11，其似乎在确定疾病的严重程度中起主要作用，以及DQ序列，其与抗Topo I抗体的发展相关。
SSc is an autoimmune connective tissue disease in which strong HLA associations have not been described. Anti-topo I antibodies are recognized, in gen- eral, in SSc patients with diffuse cutaneous involvement, whereas anti-ACAs are found in individuals with limited cutaneous involvement. We studied 35 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.