학술논문
X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
Document Type
Author
Abolhassani, Hassan; Vosughimotlagh, Ahmad; Asano, Takaki; Landegren, Nils, 1986; Boisson, Bertrand; Delavari, Samaneh; Bastard, Paul; Aranda-Guillen, Maribel; Wang, Yating; Zuo, Fanglei; Sardh, Fabian; Marcotte, Harold; Du, Likun; Zhang, Shen-Ying; Zhang, Qian; Rezaei, Nima; Kampe, Olle; Casanova, Jean-Laurent; Hammarstrom, Lennart; Pan-Hammarstrom, Qiang
Source
Journal of Clinical Immunology. 42(1):1-9
Subject
Language
English
ISSN
0271-9142
Abstract
Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk.Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI).Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry.Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient.Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively.