A Summary on the Genetics of Systemic Lupus Erythematosus, Rheumatoid Arthritis, Systemic Sclerosis, and Sj ögren’s Syndrome

AbstractSystemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and Sj ögren’s syndrome are four major autoimmune rheumatic diseases characterized by the presence of autoantibodies, caused by a dysregulation of the immune system that leads to a wide variety of clinical manifestations. These conditions present complex etiologies strongly influenced by multiple enviro nmental and genetic factors. The human leukocyte antigen (HLA) region was the first locus identified to be associated and still represents the strongest susceptibility factor for each of these conditions, particularly the HLA class II genes, includingDQA1,DQB1, andDRB1, but class I genes have also been associated. Over the last two decades, the genetic component of these disorders has been extensively investigated and hundreds of non-HLA risk genetic variants have been uncovered. Furthermore, it is widely accepted that autoimmune rheumatic diseases share molecular disease pathways, such as the interferon (IFN) type I pathways, which are reflected in a common genetic background. Some examples of well-known pleiotropic loci for autoimmune rheumatic diseases are the HLA region,DNASEL13,TNIP1, andIRF5, among others. The identification of the causal molecular mechanisms behind the genetic associations is still a challenge. However, recent advances have been achieved through mouse models and functional studies of the loci. Here, we provide an updated overview of the genetic architecture underlying the...
Source: Clinical Reviews in Allergy and Immunology - Category: Allergy & Immunology Source Type: research