Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant.
Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant.
复制标题
与狼疮抗凝剂相关的主要组织相容性复杂等位基因的分子分析。
DOI：
10.1172/jci115158
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Reveille,JD
中科院分区：
文献类型：
--
作者：
Arnett,FC;Olsen,ML;Anderson,KL;Reveille,JD
磷脂自身抗体（阿帕）常发生在系统性红斑狼疮（SLE）和其他自身免疫性疾病中，易发生血管内血栓。应用限制性片段长度多态性（RFLP）技术检测了20例阿帕患者的主要组织相容性复合体（MHC）Ⅱ类等位基因（HLA-DR和DQ）。与HLA-DR 5和-DR 4单倍型连锁的HLA-DQw 7（DQB 1 *0301）出现在70%中，并且与139个种族匹配的正常对照相比显著增加（P = 0.002，P校正[pc] = 0.05，比值比[OR] = 5.1）。此外，与不伴阿帕但伴其他自身抗体（包括抗Ro和La）的患者相比，伴阿帕的SLE患者HLA-DQw 7的频率显著升高（P = 0.0001，pc = 0.002，OR = 10.7），抗Ro单药（P = 0.001，pc = 0.02，OR = 11.2），抗dsDNA（P = 0.001，pc = 0.02，OR = 7.1），可能还有抗Sm（P = 0.04，pc = NS，OR = 6.8）和抗nRNP（U1-RNP）（P = 0.01，pc = NS，OR = 7.8）。DQw 7的DQB 1 *0301等位基因显示出最强的关联，而DQA 1 *0301（45%）和DQA 1 *0501（50%）等位基因的频率与对照组没有差异。在HLA-DQB 1 *0301（DQw 7）阴性的患者中，均存在HLA-DQw 8（DQB 1 *0302）和/或HLA-DQw 6（DQB 1 *0602或DQB 1 *0603）等位基因。HLA-DQB 1 *0301链与HLA-DQ分子的第三高变区中的DQB 1 *0302、*0602和 *0603链共享相同的七个氨基酸序列。该候选“表位”可能在介导对阿帕的自身免疫应答中起作用。
Autoantibodies to phospholipids (APA) occur frequently in systemic lupus erythematosus (SLE) and other autoimmune disorders and predispose to intravascular thromboses. Major histocompatibility complex (MHC) class II alleles (HLA-DR and DQ) were determined by restriction fragment length polymorphisms (RFLP) in 20 patients with APA (lupus anticoagulant). HLA-DQw7 (DQB1*0301), linked to HLA-DR5 and -DR4 haplotypes, occurred in 70% and was significantly increased compared to 139 race-matched normal controls (P = 0.002, P corrected [pc] = 0.05, odds ratio [OR] = 5.1). Moreover, the frequency of HLA-DQw7 was significantly higher in SLE patients with APA as compared with patients without APA but with other autoantibodies, including anti-Ro and La (P = 0.0001, pc = 0.002, OR = 10.7), anti-Ro alone (P = 0.001, pc = 0.02, OR = 11.2), anti-dsDNA (P = 0.001, pc = 0.02, OR = 7.1), and possibly anti-Sm (P = 0.04, pc = NS, OR = 6.8) and anti-nRNP (U1-RNP) (P = 0.01, pc = NS, OR = 7.8). The DQB1*0301 allele of DQw7 showed the strongest association, while the frequencies of the DQA1*0301 (45%) and DQA1*0501 (50%) alleles did not differ from the controls. Among the HLA-DQB1*0301 (DQw7) negative patients, all possessed HLA-DQw8 (DQB1*0302) and/or HLA-DQw6 (DQB1*0602 or DQB1*0603) alleles. The HLA-DQB1*0301 chain shares an identical seven amino acid sequence with DQB1*0302, *0602, and *0603 chains in the third hypervariable region of the HLA-DQ molecule. This candidate "epitope" may play a role in mediating an autoimmune response to APA.