Czaja A J, Strettell M D, Thomson L J, Santrach P J, Moore S B, Donaldson P T, Williams R
Division of Gastroenterology and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Hepatology. 1997 Feb;25(2):317-23. doi: 10.1002/hep.510250211.
Susceptibility for type 1 autoimmune hepatitis has been associated with the major histocompatibility alleles DRB10301, DRB30101, DRB10401, and DRB40103, whereas the DRB11501 allele may protect from the disease. Our aim was to determine if these alleles or others influence clinical manifestations and prognosis. Eighty-six white patients were evaluated prospectively for immune features and outcomes. Class I alleles were determined by microlymphocytotoxicity, and class II alleles were assessed by polymerase chain reaction with sequence-specific oligonucleotide probes or sequence-specific primers. One hundred two white, normal subjects were typed in the same fashion. Patients with concurrent immunologic diseases were more commonly positive for DRB40103 than patients without these features (68% vs. 38%, P = .01). DRB10301 (86% vs. 45%, P = .008) and the DRB10301-DRB30101 haplotype (79% vs. 42%, P = .02) occurred more commonly in patients who deteriorated during corticosteroid therapy. In contrast, DRB10401 and the DRB10401-DRB40103 haplotype were associated with a lower frequency of death from liver failure or the need for transplantation than patients with other alleles (0% vs. 37%, P = .03). Patients with DRB10301 differed from those with DRB10401 in that they were younger and failed treatment more commonly (27% vs. 5%, P = .04). We conclude that alleles associated with susceptibility to type 1 autoimmune hepatitis also influence its clinical features and prognosis. DRB40103 is associated with concurrent immune diseases, DRB10301 with a poor treatment response, and DRB1*0401 with a lower frequency of hepatic death or transplantation.
1型自身免疫性肝炎的易感性与主要组织相容性等位基因DRB10301、DRB30101、DRB10401和DRB40103相关，而DRB11501等位基因可能对该病具有保护作用。我们的目的是确定这些等位基因或其他等位基因是否会影响临床表现和预后。对86例白人患者进行了前瞻性免疫特征和预后评估。通过微量淋巴细胞毒性测定I类等位基因，通过聚合酶链反应和序列特异性寡核苷酸探针或序列特异性引物评估II类等位基因。以同样的方式对102名白人正常受试者进行了分型。并发免疫疾病的患者DRB40103阳性率高于无这些特征的患者（68%对38%，P = 0.01）。DRB10301（86%对45%，P = 0.008）和DRB10301-DRB30101单倍型（79%对42%，P = 0.02）在皮质类固醇治疗期间病情恶化的患者中更常见。相比之下，与其他等位基因的患者相比，DRB10401和DRB10401-DRB40103单倍型与肝衰竭死亡或移植需求的发生率较低相关（0%对37%，P = 0.03）。携带DRB10301的患者与携带DRB10401的患者不同，前者更年轻，治疗失败更常见（27%对5%，P = 0.04）。我们得出结论，与1型自身免疫性肝炎易感性相关的等位基因也会影响其临床特征和预后。DRB40103与并发免疫疾病相关，DRB10301与治疗反应差相关，DRB1*0401与肝死亡或移植发生率较低相关。
