Clinical implications of shared genetics and pathogenesis in autoimmune diseases

• Published in: Nature reviews. Endocrinology Vol. 9; no. 11; pp. 646 - 659
• Main Authors: Zhernakova, Alexandra, Withoff, Sebo, Wijmenga, Cisca
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2013; Nature Publishing Group
• Subjects: 692/420/2489/144; 692/699/2743/1313; 692/700/565; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - epidemiology; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoimmune diseases; Autoimmune Diseases - diagnosis; Autoimmune Diseases - epidemiology; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Biomarkers; Celiac disease; Development and progression; Diabetes; Endocrinology; Genetic aspects; Genetic Predisposition to Disease - genetics; Genetics; Graves disease; Health aspects; Humans; Immune system; Lupus; Lupus Erythematosus, Systemic - diagnosis; Lupus Erythematosus, Systemic - epidemiology; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Medical diagnosis; Medicine; Medicine & Public Health; Pathogenesis; Psoriasis; review-article; Rheumatoid arthritis; Risk factors; T cells; Thyroid diseases; Tumor necrosis factor-TNF; Netherlands
• ISSN: 1759-5029; 1759-5037; 1759-5037
• DOI: 10.1038/nrendo.2013.161

Many autoimmune diseases share a large proportion of their genetic background with other autoimmune diseases, which could result in common drug targets for several diseases. This Review focuses on the latest insights into the genetic factors that contribute to a range of autoimmune diseases. Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the presence of autoreactive T cells. They are caused by a complex genetic predisposition that is attributable to multiple genetic variants, each with a moderate-to-low effect size. Most of the genetic variants associated with a particular autoimmune endocrine disease are shared between other systemic and organ-specific autoimmune and inflammatory diseases, such as rheumatoid arthritis, coeliac disease, systemic lupus erythematosus and psoriasis. Here, we review the shared and specific genetic background of autoimmune diseases, summarize their treatment options and discuss how identifying the genetic and environmental factors that predispose patients to an autoimmune disease can help in the diagnosis and monitoring of patients, as well as the design of new treatments. Key Points Autoimmune diseases share a large proportion of their genetic background; shared genes and pathways might serve as common drug targets across diseases Genetic studies are discovering new pathways relevant to autoimmune diseases Determining genetic profiles for common autoimmune diseases could improve understanding of the underlying pathways and help identify novel drug targets for less common and rare autoimmune diseases Genetic profiling will help identify individuals at risk of autoimmune diseases, which is important for timely diagnosis and treatment Genetic, microRNA, metabolomic, microbiome and autoimmune profiles can serve as biomarkers for monitoring disease progression and response to treatment