Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut

Abstract

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.

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

“…The primary function of HLA-DR is to present peptide antigens, potentially foreign in origin, to the immune system for the purpose of eliciting or suppressing T-helper responses that eventually lead to the production of antibodies against the same peptide antigen [56]. In the instance of an infection, the peptide is bound into a DR molecule and presented to a few T-cell receptors found on T-helper cells.…”

Prevalence of autoimmune diseases in an admixed population of patients with type 1 diabetes: a multicenter study in Brazil

“…However we can not rule out the interplay between genetic predisposition and enviromental factors as well the participation of other genes outside the HLA region [ 33 , 34 ]. Recently the participation of the dysbiosis in this pathogenic process has been pointed out [ 37 ].…”

Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease

“…Analyses in children with a double diagnosis also demonstrated a strong positive correlation between GAL-1 and composite estimates of several cytokines, with the strongest positive correlation found when combining IL-1β, IL-6, and TNF-α, but also a positive correlation to Th1-associated IFN-γ and the T1D-associated immune marker visfatin. T1D and CeD share several common risk factors, including common risk-associated human leukocyte antigen (HLA)-haplotypes, and microbiotic alterations in the gut [ 49 ]. However, there are both common and unique risk factors for T1D and CeD, and it may be that children with a double diagnose present certain HLA-haplotypes and lack of gut microbiota diversity to a larger degree than those with only one diagnosis.…”