title: Genetic disorders with immune dysregulation.
abstract: We summarize the clinical presentation and molecular basis of a unique group of congenital immunodeficiency disorders in which defects in immune tolerance mechanisms result in severe autoimmunity. Patients with severe, familial forms of multi-organ autoimmunity have been recognized and clinically described for more than 40 years (Clin Exp Immunol 1: 119-128, 1966; Clin Exp Immunol 2: 19-30, 1967). Some are characterized primarily by autoimmunity and others by autoimmunity combined with susceptibility to specific infectious organisms. The first mechanistic understanding of these disorders began to emerge approximately 10 years ago with the initial identification of causative genes. As a result, our understanding of how immune tolerance is established and maintained in humans has expanded dramatically. Data generated over the last 3-4 years including identification of additional gene defects and functional characterization of each identified gene product in human and animal models have added clarity. This, in turn, has improved our ability to diagnose and effectively treat these severe, life-threatening disorders. Inherited disorders characterized by immune dysregulation have dramatically expanded our understanding of immune tolerance mechanisms in humans. Recognition and diagnosis of these disorders in the clinic allows timely initiation of life-saving therapies that may prevent death or irreversible damage to vital organs.
authors: Department of Sciences for Woman and Child's Health, Anna Meyer Children's Hospital, University of Florence, Florence, Italy.
authors: Eleonora
authors: E
authors: Gambineri
authors: Troy R
authors: TR
authors: Torgerson
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D019937:Diagnostic Techniques and Procedures; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016753:Interleukin-10 / Q000172:deficiency; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency; D008297:Male; D051379:Mice; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000628:therapy; D053701:Receptors, Interleukin-10 / Q000172:deficiency; D012097:Repressor Proteins / Q000172:deficiency; D050799:STAT5 Transcription Factor / Q000172:deficiency; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency; D000096927:AIRE Protein
chemical_list: D051858:Forkhead Transcription Factors; D016753:Interleukin-10; D053645:Interleukin-2 Receptor alpha Subunit; D053701:Receptors, Interleukin-10; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000096927:AIRE Protein; C418974:FOXP3 protein, human; C508017:IL2RA protein, human; C494095:STAT5B protein, human; C432966:ITCH protein, human