Year: 2020
Type: article
Study design: Case Report
Abstract: IRAK4 deficiency is an inborn error of immunity predisposing patients to invasive pyogenic infections. Currently, there is no established simple assay that enables precise characterization of IRAK4 mutant alleles in isolation. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune condition that is characterized by psychiatric symptoms, involuntary movement, seizures, autonomic dysfunction, and central hypoventilation. It typically occurs in adult females associated with tumors. Only a few infantile cases with anti-NMDAR encephalitis have been so far reported. We identified a 10-month-old boy with IRAK4 deficiency presenting with anti-NMDAR encephalitis and human herpes virus 6 (HHV6) reactivation. The diagnosis of IRAK4 deficiency was confirmed by the identification of compound heterozygous mutations c.29_30delAT (p.Y10Cfs*9) and c.35G>C (p.R12P) in the IRAK4 gene, low levels of IRAK4 protein expression in peripheral blood, and defective fibroblastic cell responses to TLR and IL-1 (TIR) agonist. We established a novel NF-κB reporter assay using IRAK4-null HEK293T, which enabled the precise evaluation of IRAK4 mutations. Using this system, we confirmed that both novel mutations identified in the patient are deleterious. Our study provides a new simple and reliable method to analyze IRAK4 mutant alleles. It also suggests the possible link between inborn errors of immunity and early onset anti-NMDAR encephalitis.
Source: Journal of Clinical Immunology
Authors: Shiho Nishimura, Yoshiyuki Kobayashi, Hidenori Ohnishi, Kunihiko Moriya, Miyuki Tsumura, Sonoko Sakata, Yoko Mizoguchi, Hidetoshi Takada, Zenichiro Kato, Vanessa Sancho-Shimizu, Capucine Picard, Sarosh R. Irani, Osamu Ohara, Jean-Laurent Casanova, Anne Puel, Nobutsune Ishikawa, Satoshi Okada, Masao Kobayashi
Institutions: Hiroshima University, Gifu University, Inserm, Tohoku University, Human Genetic of Infectious Diseases, Institut des Maladies Génétiques Imagine, University of Tsukuba, Imperial College London, Hôpital Necker-Enfants Malades, Sorbonne Paris Cité, Assistance Publique – Hôpitaux de Paris, Université Paris Descartes, University of Oxford, Kazusa DNA Research Institute, Howard Hughes Medical Institute, Rockefeller University, Japanese Red Cross Society, Japan
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,860
Awards: Characterization of the mechanism of combined immunodeficiency due to ubiquitin modification abnormalities, Multi-OMICS approaches to investigate molecular pathogenesis of primary immune deficiency, G3112400006, G4475493587, Investigation of molecular mechanism and therapeutic target of Chronic Mucocutaneous Candidiasis, Characterization of etiology of primary immunodeficiency by focusing on host susceptibility to specific pathogens, The immunobiology of autoantibody-mediated diseases of the central nervous system., Gene editing for the study of severe congenital neutropenia, Development of novel gene therapy system for genetic hematological disorders by using stealth RNA vector, The immunobiology of autoantibody-mediated diseases of the central nervous system.
OpenAlex ID: W3086395081