Major histocompatility complex haplotypic associations in Felty's syndrome and large granular lymphocyte syndrome are secondary to allelic association with HLA-DRB1*0401
Major histocompatility complex haplotypic associations in Felty's syndrome and large granular lymphocyte syndrome are secondary to allelic association with HLA-DRB1*0401
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DOI：
10.1093/rheumatology/39.4.393
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发表时间：
2000-04-01
期刊：
影响因子：
5.5
通讯作者：
Lanchbury, JS
中科院分区：
文献类型：
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作者：
Coakley, G;Brooks, D;Lanchbury, JS
目标。目的：探讨HLAⅰ类在Felty综合征（FS）和大颗粒淋巴细胞综合征（LGL）易感性中的作用。研究对象为50例高加索FS患者和55例LGL综合征患者，其中26例有关节炎，29例无关节炎。采用分子方法进行完整的HLA I类和HLA- dr分型，包括相关的DRB1*04亚型分型。与78名未选择的健康高加索人对照和另外29名DRB1*0401+个体进行比较。HLA-A*02与FS之间存在显著相关性[比值比（OR） 3.9, 95%可信区间（95% CI） 1.8 ~ 8.4, P = 0.0004]。在B位点，B*44与LGL与关节炎有相关性[OR 3.5 (1.3-9.2), P = 0.01]。HLA Cw*0501与FS有相关性[OR 4 (1.7 ~ 9.2) P = 0.0008]。FS和LGL伴关节炎的扩展单倍型HLA-A*02；B*44;Cw*0501；DRB1*0401显著相关[OR 9.5 (2.6-35), P = 0.0001；OR为4.6 (1-22.4),P = 0.05]。HLA I类或II类与无关节炎的LGL无相关性。与HLA-DRB1*0401+对照相比，所有等位基因和单倍型关联均消失。HLA相关性最强的是FS患者HLA- drb1 *0401 [OR 27.9 (10.3-75.5), P = 10(-13)]， LGL关节炎患者HLA- drb1 *0401 [OR 35.4 (9.6-131.3), P = 10(-10)]。本文报道的与FS相关的主要组织相容性位点（MHC）是由于与HLA-DRB1*0401的连锁不平衡。伴关节炎的LGL综合征与FS表现出相同的II级相关性，尽管两者在I级区域可能存在细微的免疫遗传学差异。在许多关于FS和类风湿关节炎的研究中报道的一个扩展单倍型（概括为HLA-A*02；Cw*0501; B*44;TNFbS;TNFa6;TNFd4;C4A*3;C4BQ*0;DRB1*0401;DQB1*0301）可能是由于与HLA-DRB1*0401有很强的原发性关联，而不是这些位点之间的遗传相互作用。
Objective. To investigate the role of HLA class I in susceptibility to Felty's syndrome (FS) and large granular lymphocyte (LGL) syndrome.Methods. Fifty caucasoid FS patients, and 55 patients with LGL syndrome, of whom 26 had arthritis and 29 did not, were studied. Complete HLA class I and HLA-DR typing including, where relevant, DRB1*04 subtyping was carried out by molecular methods. Comparison was made with 78 unselected healthy caucasoid controls and a further 29 DRB1*0401+ individuals.Results. A significant association was found between HLA-A*02 and FS [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 1.8-8.4, P = 0.0004]. At the B locus, there was an association between B*44 and LGL with arthritis [OR 3.5 (1.3-9.2), P = 0.01]. For HLA Cw*0501, there was an association with FS [OR 4 (1.7-9.2) P = 0.0008]. For both FS and LGL with arthritis, the extended haplotype HLA-A*02;B*44;Cw*0501;DRB1*0401 was significantly associated [OR 9.5 (2.6-35), P = 0.0001; OR 4.6 (1-22.4), P = 0.05, respectively]. There was no association between HLA class I or II and LGL without arthritis. All the allelic and haplotypic associations were lost on comparison with HLA-DRB1*0401+ controls. The strongest HLA association was with HLA-DRB1*0401 for FS [OR 27.9 (10.3-75.5), P = 10(-13)], and LGL with arthritis [OR 35.4 (9.6-131.3), P = 10(-10)].Conclusions. The major histocompatibility locus (MHC) associations with FS reported here are due to linkage disequilibrium with HLA-DRB1*0401. LGL syndrome with arthritis shows identical class II associations with FS, although there may be subtle immunogenetic differences between the two in the class I region. One of the extended haplotypes reported in a number of studies for FS and rheumatoid arthritis (summarized as HLA-A*02;Cw*0501; B*44;TNFbS;TNFa6;TNFd4;C4A*3;C4BQ*0;DRB1*0401;DQB1*0301) is likely to be attributable to strong primary association with HLA-DRB1*0401, rather than to epistatic interaction between these loci.