title: Transient hemophagocytosis with deficient cellular cytotoxicity, monoclonal immunoglobulin M gammopathy, increased T-cell numbers, and hypomorphic NEMO mutation.
abstract: X-linked osteopetrosis, anhydrotic ectodermal dysplasia, and immunodeficiency (XL-O-EDA-ID) is a disorder that is caused by hypomorphic mutations in the nuclear factor kappaB essential modulator (NEMO). These mutations lead to an impaired NF-kappaB activation. In vitro analyses and studies in animal models show that inhibition of NF-kappaB leads to a decrease of cytokine production and T-cell proliferation. Patients classically display poor or delayed inflammatory response to infections. We describe a boy with XL-O-EDA-ID, 1167-1168insC NEMO mutation, and recurrent infections. In early infancy, he experienced hemophagocytosis with transient deficiency of natural killer activity. Increased immunoglobulin M levels in blood resulted from a monoclonal immunoglobulin M gammopathy. Blood T-cell numbers were constantly increased, most probably resulting from a peripheral T-cell expansion. Our observations suggest that patients with hypomorphic NEMO mutations and repeated infections may experience inflammatory dysregulation.
authors.affiliation: Division of Immunology/Hematology/BMT, University Children's Hospital, Zurich, Switzerland.
authors.forename: Jana M
authors.initials: JM
authors.lastname: Pachlopnik Schmid
authors.forename: Sonja A
authors.initials: SA
authors.lastname: Junge
authors.forename: Johann Peter
authors.initials: JP
authors.lastname: Hossle
authors.forename: E Marion
authors.initials: EM
authors.lastname: Schneider
authors.forename: Eddy
authors.initials: E
authors.lastname: Roosnek
authors.forename: Reinhard A
authors.initials: RA
authors.lastname: Seger
authors.forename: Tayfun
authors.initials: T
authors.lastname: Gungor
mesh_terms: D001424:Bacterial Infections / Q000150:complications; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D004476:Ectodermal Dysplasia / Q000150:complications* / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000150:complications*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000150:complications* / Q000276:immunology; D051550:I-kappa B Kinase / Q000235:genetics*; D007075:Immunoglobulin M / Q000032:analysis*; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000276:immunology; D018655:Lymphocyte Count; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications*; D008297:Male; D009154:Mutation; D010022:Osteopetrosis / Q000150:complications* / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C491731:IKBKG protein, human; D007075:Immunoglobulin M; D051550:I-kappa B Kinase