Laboratorio de investigación en Genética de enfermedades complejas, Hospital Clínicos San Carlos, IdISSC, Madrid, Spain.
Laboratorio de investigación en Genética de enfermedades complejas, Hospital Clínicos San Carlos, IdISSC, Madrid, Spain.
Int Rev Cell Mol Biol. 2021;358:47-83. doi: 10.1016/bs.ircmb.2020.09.009. Epub 2020 Nov 11.
The Human Leukocyte Antigen (HLA) has a crucial role in the development and pathogenesis of coeliac disease (CD). The genes HLA-DQA1 and HLA-DQB1, both lying in this region and encoding the HLA-DQ heterodimer, are the main genetic predisposing factors to CD. Approximately 90% of CD patients carry the heterodimer HLA-DQ2.5, leaving only a small proportion of patients with lower risk heterodimers (HLA-DQ8, HLA-DQ2.2 or HLA-DQ7.5). These HLA-DQ molecules act as receptors present in the surface of antigen presenting cells and show high affinity for deamidated gluten peptides, which bind and present to CD4 T cells. This triggers the immunological reaction that evolves into CD. Since specific HLA genetics is present in almost the totality of CD patients, HLA typing has a very high negative predictive value, and it can be used to support diagnosis in specific scenarios. HLA risk has been associated to different CD-related features, such as age at onset, clinical outcomes, antibody levels and grade of histological lesion; but further research is needed. HLA-DQ genotypes have been also suggested to modulate the composition of the gut microbiota.
人类白细胞抗原（HLA）在乳糜泻（CD）的发展和发病机制中起着关键作用。位于该区域并编码 HLA-DQ 异二聚体的基因 HLA-DQA1 和 HLA-DQB1 是 CD 的主要遗传易感因素。大约 90%的 CD 患者携带 HLA-DQ2.5 异二聚体，只有一小部分患者携带风险较低的异二聚体（HLA-DQ8、HLA-DQ2.2 或 HLA-DQ7.5）。这些 HLA-DQ 分子作为存在于抗原呈递细胞表面的受体，对脱酰胺谷氨酰胺肽具有高亲和力，这些肽结合并呈递给 CD4 T 细胞。这引发了演变成 CD 的免疫反应。由于几乎所有 CD 患者都存在特定的 HLA 遗传学，因此 HLA 分型具有非常高的阴性预测值，可用于在特定情况下支持诊断。HLA 风险与 CD 相关的不同特征有关，如发病年龄、临床结局、抗体水平和组织学病变程度；但还需要进一步研究。HLA-DQ 基因型也被认为可以调节肠道微生物群的组成。
