多发性硬化症：加倍 MHC。

Multiple sclerosis: doubling down on MHC.

机构信息

Neuroimmunology and Multiple Sclerosis Research, Neurology Clinic, Frauenklinikstrasse 26, 8091 Zurich, University Hospital Zurich, University Zurich, Switzerland.

出版信息

Trends Genet. 2021 Sep;37(9):784-797. doi: 10.1016/j.tig.2021.04.012. Epub 2021 May 15.

DOI:10.1016/j.tig.2021.04.012

PMID:34006391

Abstract

Human leukocyte antigen (HLA)-encoded surface molecules present antigenic peptides to T lymphocytes and play a key role in adaptive immune responses. Besides their physiological role of defending the host against infectious pathogens, specific alleles serve as genetic risk factors for autoimmune diseases. For multiple sclerosis (MS), an autoimmune disease that affects the brain and spinal cord, an association with the HLA-DR15 haplotype was described in the early 1970s. This short opinion piece discusses the difficulties of disentangling the details of this association and recent observations about the functional involvement of not only one, but also the second gene of the HLA-DR15 haplotype. This information is not only important for understanding the pathomechanism of MS, but also for antigen-specific therapies.

摘要

人类白细胞抗原（HLA）编码的表面分子将抗原肽呈递给 T 淋巴细胞，并在适应性免疫反应中发挥关键作用。除了其防御宿主免受感染性病原体的生理作用外，特定的等位基因还作为自身免疫性疾病的遗传风险因素。对于多发性硬化症（MS），这是一种影响大脑和脊髓的自身免疫性疾病，早在 20 世纪 70 年代就描述了与 HLA-DR15 单倍型的关联。这篇简短的观点文章讨论了阐明这种关联细节的困难，以及最近关于 HLA-DR15 单倍型不仅一个，而且第二个基因的功能参与的观察结果。这些信息不仅对于理解 MS 的发病机制很重要，对于抗原特异性治疗也很重要。