Omenn syndrome: Inflammation in leaky severe combined immunodeficiency

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 TH2 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 γ, IL-7 receptor α, ARTEMIS, and DNA ligase 4. This new information revealed OS is a distinct inflammatory process that can be associated with genetically diverse leaky SCIDS.

Key words: Immunodeficiency, Omenn syndrome, mutation, SCID

Abbreviations used: ADA, Adenosine deaminase, AIRE, AutoImmune REgulator, CHARGE, Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and deafness, CHD7, Chromodomain helicase DNA binding protein 7, CHH, Cartilage hair hypoplasia, DCLRE1C, DNA cross-link repair 1C protein, LIG4, DNA ligase 4, OS, Omenn syndrome, RAG, Recombination activating gene, RMRP, RNA component of mitochondrial RNA processing endoribonuclease, SCID, Severe combined immunodeficiency, Treg, Regulatory T