X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia

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....

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Veröffentlicht in:Journal of clinical immunology 2022-01, Vol.42 (1), p.1-9
Hauptverfasser: Abolhassani, Hassan, Vosughimotlagh, Ahmad, Asano, Takaki, Landegren, Nils, Boisson, Bertrand, Delavari, Samaneh, Bastard, Paul, Aranda-Guillén, Maribel, Wang, Yating, Zuo, Fanglei, Sardh, Fabian, Marcotte, Harold, Du, Likun, Zhang, Shen-Ying, Zhang, Qian, Rezaei, Nima, Kämpe, Olle, Casanova, Jean-Laurent, Hammarström, Lennart, Pan-Hammarström, Qiang
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Sprache:eng
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Zusammenfassung: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.
ISSN:0271-9142
1573-2592
1573-2592
DOI:10.1007/s10875-021-01151-y