Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Journal of clinical immunology, 2022-01, Vol.42 (1), p.1-9

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2022

Link zum Volltext

Quelle

SpringerLink (Online service)

Beschreibungen/Notizen

• 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.