Berryman Meghan A, Ilonen Jorma, Triplett Eric W, Ludvigsson Johnny
Triplett Laboratory, Institute of Food and Agricultural Sciences, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, United States.
Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.
Front Immunol. 2023 Sep 26;14:1270488. doi: 10.3389/fimmu.2023.1270488. eCollection 2023.
Human leukocyte antigen (HLA) genes are associated with more diseases than any other region of the genome. Highly polymorphic HLA genes produce variable haplotypes that are specifically correlated with pathogenically different autoimmunities. Despite differing etiologies, however, many autoimmune disorders share the same risk-associated HLA haplotypes often resulting in comorbidity. This shared risk remains an unanswered question in the field. Yet, several groups have revealed links between gut microbial community composition and autoimmune diseases. Autoimmunity is frequently associated with dysbiosis, resulting in loss of barrier function and permeability of tight junctions, which increases HLA class II expression levels and thus further influences the composition of the gut microbiome. However, autoimmune-risk-associated HLA haplotypes are connected to gut dysbiosis long before autoimmunity even begins. This review evaluates current research on the HLA-microbiome-autoimmunity triplex and proposes that pre-autoimmune bacterial dysbiosis in the gut is an important determinant between autoimmune comorbidities with systemic inflammation as a common denominator.
人类白细胞抗原（HLA）基因比基因组的任何其他区域都与更多疾病相关。高度多态性的HLA基因产生可变单倍型，这些单倍型与致病性不同的自身免疫性疾病存在特定关联。然而，尽管病因不同，但许多自身免疫性疾病共享相同的风险相关HLA单倍型，这常常导致共病。这种共同的风险在该领域仍然是一个未解决的问题。然而，几个研究小组已经揭示了肠道微生物群落组成与自身免疫性疾病之间的联系。自身免疫性疾病常常与生态失调相关，导致屏障功能丧失和紧密连接的通透性增加，这会增加HLA II类分子的表达水平，从而进一步影响肠道微生物群的组成。然而，与自身免疫性疾病风险相关的HLA单倍型在自身免疫性疾病开始之前很久就与肠道生态失调有关。这篇综述评估了目前关于HLA-微生物群-自身免疫性疾病三元组的研究，并提出肠道中自身免疫性疾病发生前的细菌生态失调是以全身炎症为共同特征的自身免疫性疾病共病的一个重要决定因素。
