title: Pathologic Findings in NEMO Deficiency: A Surgical and Autopsy Survey.
abstract: Hypomorphic mutations in nuclear factor κB (NF-κB) essential modulator (NEMO), encoded by IKBKG, lead to a variable combined immunodeficiency, which puts patients at risk of early death from infectious complications. The spectrum of clinical manifestations includes inflammatory disorders, especially colitis. Because of the multiple complications of NEMO deficiency, a variety of biopsy, excisional, and autopsy materials from these patients may be subject to pathologic examination. Therefore, using samples from a cohort of patients with this disorder, we aimed to survey the pathologic spectrum of NEMO deficiency and search for correlations between specific genotypes and phenotypes. Clinical and laboratory data, mutation analysis, and pathology from 13 patients were examined, including 6 autopsies. No specific genotype-pathology correlation was identified. However, we confirmed an association between ectodermal dysplasia and inflammatory conditions. We found no characteristic pathology to identify patients with NEMO deficiency; therefore, history, physical examination, and specific infections must remain the clues to suggest the diagnosis. Variability among patients and by infection makes the pathologic recognition of NEMO deficiency challenging.
authors.affiliation: 1 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Huppmann
authors.affiliation: 2 Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.|3 University of South Florida, Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, St Petersburg, FL, USA.
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Leiding
authors.affiliation: 2 Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Hsu
authors.affiliation: 1 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: 2 Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.affiliation: 1 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: 2 Laboratory of Clinical Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: C491731:IKBKG protein, human; D051550:I-kappa B Kinase
keywords: NEMO; NF-κB; autopsy; immunodeficiency; mycobacteria; pathology