title: Correlating interleukin-12 stimulated interferon-γ production and the absence of ectodermal dysplasia and anhidrosis (EDA) in patients with mutations in NF-κB essential modulator (NEMO).
abstract: OBJECTIVE
  Patients with hypomorphic mutations in Nuclear Factor-κB Essential Modulator (NEMO) are immunodeficient (ID) and most display ectodermal dysplasia and anhidrosis (EDA). We compared cytokine production by NEMO-ID patients with and without EDA.
  
  
  METHODS
  PBMCs of NEMO-ID patients, four with EDA carrying E315A, C417R, D311N and Q403X, and three without EDA carrying E315A, E311_L333del and R254G, were cultured with PHA, PHA plus IL-12p70, LPS, LPS plus IFN-γ, TNF and IL-1β. The production of various cytokines was measured in the supernatants. Fifty-nine healthy individuals served as controls.
  
  
  RESULTS
  PBMCs of NEMO-ID patients without EDA produce subnormal amounts of IFN-γ after stimulation with PHA, but normal amounts of IFN-γ after PHA plus IL-12p70. In contrast, IFN-γ production by patients with EDA was low in both cases. Patients with EDA also generate lower PHA-stimulated IL-10 and IL-1β than controls, whereas the production of these cytokines by patients without EDA was normal.
  
  
  CONCLUSIONS
  Responses of PBMCs in NEMO-ID patients with EDA to PHA with and without IL-12p70 appear less robust than in NEMO-ID patients without EDA. This possibly indicates a better preserved NEMO function in our patients without EDA.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands, m.h.haverkamp@lumc.nl.
authors.forename: Margje H
authors.initials: MH
authors.lastname: Haverkamp
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Marciano
authors.forename: David M
authors.initials: DM
authors.lastname: Frucht
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004476:Ectodermal Dysplasia / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D061251:Primary Cell Culture; D000081207:Primary Immunodeficiency Diseases; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C491731:IKBKG protein, human; C508609:IL10 protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D051550:I-kappa B Kinase