Genomics and the Multifactorial Nature of Human Autoimmune Disease

• Published in: The New England journal of medicine Vol. 365; no. 17; pp. 1612 - 1623
• Main Authors: Cho, Judy H, Gregersen, Peter K
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 27.10.2011
• Subjects: Adaptive Immunity - physiology; Antigens; Autoimmune diseases; Autoimmune Diseases - genetics; Bacteria - immunology; Biological and medical sciences; Cytokines; Cytokines - metabolism; Defects; Deoxyribonucleic acid; Diabetes; DNA; Gene loci; General aspects; Genetic Diseases, Inborn; Genetics; Genomics; HLA Antigens - genetics; Humans; Immune system; Immunity, Innate - genetics; Immunity, Innate - physiology; Inflammation - immunology; Inflammatory bowel disease; Kinases; Lymphocytes; Medical sciences; Mutation; Pathogenesis; Proteins; Psoriasis; Quantitative Trait, Heritable; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; T-Lymphocytes - metabolism; Transcription factors; Human; Medicine; Immunopathology; Autoimmune disease; Genome; Genomics
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMra1100030

This article reviews the many new insights into autoimmune disease brought about through genomic investigations. The major autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes mellitus, psoriasis, and inflammatory bowel disease, share epidemiologic, clinical, and therapeutic features. In each of these diseases, chronic and often intermittent inflammation contributes over time to the destruction of target organs that house inciting antigens or are the sites of immune-complex deposition. For some of these disorders, such as inflammatory bowel disease, the contribution of autoimmune mechanisms is questioned, but the overlap of genetic associations that have been identified during the past 5 years suggests a shared immune pathogenesis. At the same time, genetic data . . .