Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population.
Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population.
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DOI：
10.1371/journal.pone.0146048
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Nakane S
中科院分区：
文献类型：
--
作者：
Maeda Y;Migita K;Higuchi O;Mukaino A;Furukawa H;Komori A;Nakamura M;Hashimoto S;Nagaoka S;Abiru S;Yatsuhashi H;Matsuo H;Kawakami A;Yasunami M;Nakane S
抗神经节烟碱乙酰胆碱受体（gAChR）抗体在自身免疫性疾病以及患有自身免疫性自主神经节病的患者中观察到。然而，抗gAChR抗体的遗传背景尚不清楚。在这里，我们调查了HLA等位基因在自身免疫性肝炎（AIH）患者有或无抗gAChR抗体。对260例1型自身免疫性肝炎（AIH）患者的基因组DNA进行HLA-A、B、DRB 1和DQB 1基因分型。用荧光素酶免疫沉淀系统检测AIH患者血清中抗gAChR抗体，并检测有或无抗gAChR抗体患者的等位基因关联。我们在11.5%（30/260）的AIH患者中检测到抗α3或β4 gAChR抗体。在AIH患者中，HLA-A、B DQB 1等位基因与抗gAChR抗体阳性无显著相关性。而HLA-DRB 1 *0403等位基因在抗gAChR抗体阳性的AIH患者中的频率显著高于无抗gAChR抗体的AIH患者。根据是否存在抗gAChR抗体，日本AIH患者HLA-DRB 1 *0403等位基因的频率不同。我们的研究结果表明，特定的HLA II类分子可能控制抗gAChR抗体的发展，在自身免疫反应gAChR。
Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies. Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies. We detected anti-α3 or -β4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies. The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR.