Heresbach D, Alizadeh M, Reumaux D, Colombel J F, Delamaire M, Danze P M, Gosselin M, Genetet B, Bretagne J F, Semana G
Service d'Hépato-Gastroentérologie, CHRU Pontchaillou, Rennes, France.
J Autoimmun. 1996 Dec;9(6):777-84. doi: 10.1006/jaut.1996.0100.
The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n = 91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n = 200) were included. HLA-DRB1*03 was less frequent in UC patients than in healthy controls (8% vs 28%, PC < 0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively, (PC < 0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.
溃疡性结肠炎（UC）的发病机制尚未阐明，但一些观点表明遗传因素与之相关。在候选基因中，编码HLA II类基因型的基因在UC中已得到广泛研究；然而，数据不一致可能归因于以非典型抗中性粒细胞胞浆抗体（p-ANCA）等免疫标志物为特征的异质性，或者归因于纳入了或多或少难治性的UC。我们研究的目的是根据p-ANCA状态评估HLA II类和TAP基因标志物在识别不同临床形式UC方面的价值。纳入了有UC病史的非亲属患者（n = 91）和无个人或家族炎症性肠病（IBD）病史的健康对照者（n = 200）。UC患者中HLA-DRB1*03的频率低于健康对照者（8%对28%，P<0.03）。未发现与任何TAP基因型相关。此外，无论是在整个UC患者组（38%对28%）还是在p-ANCA阳性患者亚组（30%）中，均未发现与HLA-DR2特异性相关。本研究中最一致的发现是，一些基因标志物可能是UC患者难治性的特征。无论p-ANCA状态如何，HLA-DR2均与预后不良相关。在HLA-DR2组和非HLA-DR2组中，分别有55%和27%的患者接受了结肠切除术（P<0.05）。此外，在非HLA-DR2患者中，p-ANCA可能有助于识别预后更差的患者。我们的结果证实了考虑到疾病难治性进行基因研究以确定UC遗传易感性的价值。它们不支持p-ANCA是UC遗传易感性亚临床标志物的假设。
