title: Omenn syndrome: inflammation in leaky severe combined immunodeficiency.
abstract: Omenn syndrome (OS) was reported until recently as a distinct form (phenotype and genotype) of severe combined immunodeficiency (SCID). Similar to other patients with SCID, patients with OS present early in infancy with viral or fungal pneumonitis, chronic diarrhea, and failure to thrive. Unlike typical SCID, patients with OS have enlarged lymphoid tissue, severe erythroderma, increased IgE levels, and eosinophilia. The inflammation observed in these patients is believed to be triggered by clonally expanded T cells, which are predominantly of the T(H)2 type. These abnormal T cells, in the absence of proper regulation by other components of the immune system, secrete a host of cytokines that promote autoimmune as well as allergic inflammation. The emergence of these T-cell clones occurs in patients with hypomorphic mutations in recombination activating gene 1 or 2, but not in patients with deleterious mutations in these enzymes which render them inactive. Recently, OS was also identified in a growing list of other leaky SCIDs with mutations in RNA component of mitochondrial RNA processing endoribonuclease, adenosine deaminase, IL-2 receptor gamma, IL-7 receptor alpha, ARTEMIS, and DNA ligase 4. This new information revealed OS is a distinct inflammatory process that can be associated with genetically diverse leaky SCIDS.
authors.affiliation: Istituto Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D003873:Dermatitis, Exfoliative / Q000235:genetics / Q000276:immunology; D004802:Eosinophilia / Q000235:genetics / Q000276:immunology; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D009154:Mutation / Q000276:immunology; D010641:Phenotype; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D007073:Immunoglobulin E