Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease
Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease
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DOI：
10.1016/s0016-5085(00)70209-5
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发表时间：
2000-02-01
期刊：
影响因子：
29.4
通讯作者：
Jewell, DP
中科院分区：
文献类型：
--
作者：
Orchard, TR;Thiyagaraja, S;Jewell, DP
背景与目的：与疾病易感基因相反，表型决定基因的检测需要精确的患者表型特征。炎症性肠病（IBD）中的外周关节病得到了广泛认可，并被欧洲脊柱关节病研究组归类为HL 4-B*27相关脊柱关节病。然而，以前的IBD HLA研究只显示了这种关联与轴性疾病，而不是外周关节病。我们最近报道了一种临床分类，描述了2种类型的外周关节病，根据其自然病史和关节分布进行区分。我们现在报告这些患者的免疫遗传学研究结果，并将其与其他脊柱关节病进行比较。方法：通过病例回顾和问卷调查确定IBD患者1型（n = 57）和2型（n = 45）外周关节病。通过序列特异性引物聚合酶链反应，对来自牛津郡的患者和603名对照者分配HLA-A、-B、-C、-DR和-DQ基因型。将患者结果与对照组进行比较（校正多重比较），然后根据现有假设相互比较。结果进行了比较，与一个队列的30例反应性关节炎（ReA）和16例IBD相关的强直性脊柱炎（IBD-AS）。结果如下：1型关节病与HLA-DRB 1 *0103（DR 103; DR 1的一种罕见亚型）相关的患者占33%（P < 0.0001;相对危险度[RR]，12.1），与B*35相关的患者占30%（P = 0.01; RR，2.2），与B*27相关的患者占26%（P = 0.001; RR，4.0）。相反，2型与HLA-B*44相关的占62%（P = 0.01; RR，2.1）。在ReA中发现与1型关节病相似的显著相关性，除了HLA-B*27的相关性显著更强，并且在43%中发现与DRB 1 *0101（DR 1）的相关性（P = 0.001; RR，2.2）。IBD AS仅与HLA-B*27和DRB 1 *0101相关。结论：这些数据表明，1型和2型关节病的临床分类描述了免疫遗传学上不同的实体，并建立了在多基因疾病中，基因可能决定临床表型，而不赋予整体疾病易感性（在这种情况下，HLA基因）。1型关节病在临床和免疫遗传学上与脊柱关节病相似，但不同的HLA相关性可能定义不同的表型组。2型关节病有不同的HLA相关性，可能有不同的病因。现在需要进一步的研究来证实这些关联，并阐明不同的发病机制。
Background & Aims:The detection of phenotype-determining genes as opposed to disease susceptibility genes requires precise phenotypic characterization of patients. Peripheral arthropathies in inflammatory bowel disease (IBD) are well recognized and are classified with the HL4-B*27-related spondyloarthropathies by the European Spondyloarthropathy Study Group. However, previous HLA studies in IBD have only shown this association with axial disease rather than peripheral arthropathy. We recently reported a clinical classification that describes 2 types of peripheral arthropathy, distinguished by their natural history and articular distribution. We now report the results of immunogenetic studies in these patients and compare them with other spondyloarthropathies. Methods: IBD patients with type 1 (n = 57) and type 2 (n = 45) peripheral arthropathy were identified by case note review and questionnaire. Patients and 603 controls from Oxfordshire were assigned HLA-A, -B, -C, -DR, and -DQ genotypes by sequence-specific primer polymerase chain reaction. Patient results were compared with controls (corrected for multiple comparisons), then with each other in light of existing hypotheses. The results were compared with those of a cohort of 30 patients with postenteric reactive arthritis (ReA) and 16 patients with IBD-associated ankylosing spondylitis (IBD-AS). Results: Type 1 arthropathy was associated with HLA-DRB1*0103 (DR103; a rare subtype of DR1) in 33% (P < 0.0001; relative risk [RR], 12.1), B*35 in 30% (P = 0.01; RR, 2.2), and B*27 in 26% (P = 0.001; RR, 4.0). In contrast, type 2 was associated with HLA-B*44 in 62% (P = 0.01; RR, 2.1). Similar significant associations to type 1 arthropathy were found in ReA, except that the HLA-B*27 association was significantly stronger and an association was found with DRB1*0101 (DR1) in 43%(P = 0.001; RR, 2.2). IBD-AS was associated only with HLA-B*27 and DRB1*0101. Conclusions: These data suggest that the clinical classification into type 1 and type 2 arthropathies describes immunogenetically distinct entities and establish that in polygenic disorders, genes may determine clinical phenotype without conferring overall disease susceptibility (in this case, HLA genes). Type 1 arthropathy is clinically and immunogenetically similar to the spondyloarthropathies, but different HLA associations may define phenotypically distinct groups. Type 2 arthropathy has different HLA associations and may have a different etiology. Further studies are now required to confirm these associations and to elucidate the different pathogenetic mechanisms.