Recent Advances in the Genetics of Autoimmune Disease

Abstract

Extraordinary technical advances in the field of human genetics over the past few years have catalyzed an explosion of new information about the genetics of human autoimmunity. In particular, the ability to scan the entire genome for common polymorphisms that associate with disease has led to the identification of numerous new risk genes involved in autoimmune phenotypes. Several themes are emerging. Autoimmune disorders have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders. There is also heterogeneity among subphenotypes within a disease and across major racial groups. The current crop of genetic associations are only the start of a complete catalog of genetic factors for autoimmunity, and it remains unclear to what extent common variation versus multiple rare variants contribute to disease susceptibility. The current review focuses on recent discoveries within functionally related groups of genes that provide clues to novel pathways of pathogenesis for human autoimmunity.

MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

“…T he clinical presentation of any specific autoimmune disease is the culmination of complex interactions between genetics, primary and secondary immune effector mechanisms, and environmental triggers 1,2 . Although different autoimmune diseases show discrete clinical features, there are common molecular pathways intimately involved, which ultimately define specific diseases 3,4 .…”

Autoimmune priming, tissue attack and chronic inflammation — The three stages of rheumatoid arthritis

“…44: 1593-1599 70 and 74 [2], to which one now also may add positions 11 and 13 that are also strongly associated with RA [3]. In addition, the identity of around hundred genetic loci, with minor contribution to RA susceptibility, strengthen the dogma that RA is caused by aberrant autoreactive T cells [4,5]. Even though the influence of MHC and CD4 + T cells are more validated than ever, we still search for the RA-inducing MHC class II-restricted T cells.…”

Does our Current Understanding of Immune Tolerance, Autoimmunity, and Immunosuppressive Mechanisms Facilitate the Design of Efficient Cancer Vaccines?

“…The ability of an epitope mimic to induce an autoimmune disease depends on its appropriate presentation by the host antigen presenting cells, thereby supporting the association between MHC products and autoimmune diseases [19]. Indeed, the binding association between a given MHC molecule and its peptide, whether it be a self-or foreign peptide involved in either a class I or II interaction, is a genetically controlled event.…”

“…The beauty of such a dynamic system is its capacity to respond rapidly and efficiently to appropriate challenges but its inherent drawback is the risk of attacking self tissues. When systemic autoimmune diseases develop, the targets of the autoimmune response are not random but are restricted to a small subset of antigens [19,20]. Thus, understanding the mechanisms that activate autoreative T cells in autoimmunity may facilitate the resetting of T cell activation threshold which is required for tumour rejection.…”

“…Even though that the predisposition of individuals to common autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematous, type I diabetes, and multiple sclerosis is genetically associated to certain human MHC class II molecules [19,23], the involvement of infections have been implicated in the onset and ⁄ or perpetuation of autoimmunity [24][25][26]. The assumption is that an infectious agent (e.g.…”