title: Interleukin 12 deficiency associated with recurrent infections.
abstract: A 3-yr-old female patient exhibited interleukin 12 (IL-12) deficiency that was associated with recurrent episodes of pneumococcal pneumonia with sepsis and other infections in the absence of fevers. The patient's peripheral blood mononuclear cells (PBMCs) exhibited normal proliferative responses to antigens. Immune responses, including in vivo production of antibodies to diphtheria, tetanus, or pneumococcal antigens, were normal. Ig levels and B cell and T cell phenotypes were also normal. In contrast, IL-12 p70 heterodimer production was undetectable by using supernatants of the patient's stimulated PBMCs when compared with control cells treated similarly. Although present, interferon gamma (IFN-gamma) was reduced. The addition of recombinant IFN-gamma to control cells enhanced the production of IL-12 by up to sixfold. By contrast, IL-12 was undetectable in supernatants of the patient's cells in the presence of recombinant IFN-gamma. IL-12 p40 subunit mRNA by using the patient's PBMCs after stimulation with Staphylococcus aureus Cowan strain 1 or lipopolysaccharide was also undetectable by reverse transcription-PCR when compared with control cells. Production of IL-2, IL-6, tumor necrosis factor alpha, or IFN-gamma of the patient's PBMCs after appropriate stimulation was observed. This patient has either a defect in Staphylococcus aureus Cowan strain 1-lipopolysaccharide- or staphylococcal enterotoxin A-induced signaling pathways for the activation of IL-12 p40 gene expression, or an abnormality in the IL-12 p40 gene itself.
authors.affiliation: Department of Pediatrics, University of South Florida College of Medicine/All Children's Hospital, 801 Sixth Street South, St. Petersburg, FL 33701, USA.
authors.forename: S
authors.initials: S
authors.lastname: Haraguchi
authors.forename: N K
authors.initials: NK
authors.lastname: Day
authors.forename: R P
authors.initials: RP
authors.lastname: Nelson
authors.forename: P
authors.initials: P
authors.lastname: Emmanuel
authors.forename: J E
authors.initials: JE
authors.lastname: Duplantier
authors.forename: C S
authors.initials: CS
authors.lastname: Christodoulou
authors.forename: R A
authors.initials: RA
authors.lastname: Good
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D002675:Child, Preschool; D003141:Communicable Diseases / Q000235:genetics / Q000276:immunology*; D003241:Consanguinity; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics* / Q000276:immunology; D016130:Immunophenotyping; D007179:Incest; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000145:classification / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012008:Recurrence; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015703:Antigens, CD; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma