Role of genetics in eleven of the most common autoimmune diseases in the post genome-wide association studies era.

Autoimmune diseases (ADs) are common conditions in which an individual's immune system reacts against its healthy cells. This condition is a common cause of morbidity and mortality, with an estimated prevalence ranging from 5 per 100,000 to more than 500 per 100,000. According to the National Stem Cell Foundation (NSCF), ADs are prevalent in about 4% of the world's population, which creates a burden on society due to the high treatment cost. ADs show a clear gender bias with a higher prevalence among women, occurring at a rate of 2:1 female-to-male ratio. The etiology of ADs includes genetic and environmental factors. ADs are more likely to develop in genetically susceptible individuals. The higher concordance ratio between monozygotic twins compared to dizygotic twins or other siblings validates the role of genetic factors in the pathogenesis of many ADs. ADs diagnosis includes conventional immunoassay such as indirect immunofluorescence, complement fixation, passive agglutination, autoantibodies detection, and most recent advances, including multiplex platforms such as microspots, line-blot, addressable microbeads and barcoded nanoparticles that allow multiplex parallel testing of autoantibodies. ADs treatment includes biological and synthetic drugs that block many pathways and components of the immune system, including Janus kinase (JAK) inhibitors, non-receptor tyrosine-protein kinase (TYK2), and other cytokines. Generally, recent immune-modulatory drugs used in ADs treatment are non-disease specific with broad action and are associated with many side effects like infection and malignant diseases. Furthermore, gene therapy seeks to control the levels of proinflammatory cytokine molecules and lymphocyte infiltration through the delivery and expression of therapeutic genes. Recent genomic-wide association studies (GWAS) have allowed the identification of various genetic loci associated with disease susceptibility and have revealed candidate genes that can be used in targeted therapeutics. This review summarizes recent literature on the genetic factors associated with susceptibility to the 11 most common ADs, namely: Type 1 diabetes mellitus (T1DM), Multiple sclerosis (MS), Grave's disease, Sjögren's syndrome (SS), Celiac disease, Hashimoto's thyroiditis (HT), Anti-phospholipid syndrome (APS), Autoimmune hemolytic anemia, Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), and Scleroderma (systemic sclerosis).