HLA-DRB1 the notorious gene in the mosaic of autoimmunity

Abstract

The major histocompatibility complex system is the most polymorphic gene cluster of the mammal genome. In humans, this is a genomic locus known as the human leukocyte antigen (HLA) system. The HLA encodes mostly immune-associated proteins whose main effect is the presentation of antigens to the immune cells. Thus, it is clear that it is essential for to the proper function of the immune response against pathogens and strongly implicated in the development of autoimmune diseases. Nonetheless, there are hundreds of polymorphisms of HLA-DRB1 which have been associated with different autoimmune disorders as well as with immune response to infection and vaccines. It is possible that the interaction of specific HLA with pathogenic antigens is one of the keys favoring (or protecting) toward the development of an autoimmune disease. In the era of personalized medicine, it would be of great help to build a map of the genomic risk of each individual to evaluate the risk of developing an autoimmune condition.

Predictive autoimmunity using autoantibodies: screening for anti-nuclear antibodies

“…There are other genetic [35][36][37][38] and environmental factors (such as; female gender [39][40][41], low levels of vitamin D [42][43][44], vaccines [38,45,46], infections [38,47,48] and hormones [49] that help to evoke a pro-inflammatory condition that triggers the pathogenesis of autoimmune diseases.…”

Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity

“…A large number of autoimmune diseases share several alleles of the HLA class II such as DRB1 locus. The development of specific autoantibodies is determined by DRB1 alleles leading to an abnormal response and development of full-blown autoimmune diseases (7, 8). …”

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) demonstrates distinct autoimmune and autoinflammatory disease associations according to the adjuvant subtype: Insights from an analysis of 500 cases

“…Autoimmune diseases are conditions that result from a complex interplay between genetic background and environmental triggers such as infection, dysbiosis, drugs or adjuvants [12][13][14]. Selfdirected inflammation with loss of tolerance, with dysfunction of dendritic cell, B and T cell with the induction of immune reactions against self-antigens is relatively rare [15]. Of note, the vast majority of people who are exposed to different adjuvant subtypes do not develop autoimmune phenomena.…”