tetano
Editor, Senior Moderator
J Clin Immunol
. 2021 Oct 23;1-9.
doi: 10.1007/s10875-021-01151-y. Online ahead of print.
X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
Hassan Abolhassani[SUP] 1 2 [/SUP], Ahmad Vosughimotlagh[SUP] 3 [/SUP], Takaki Asano[SUP] 4 [/SUP], Nils Landegren[SUP] 5 6 [/SUP], Bertrand Boisson[SUP] 4 7 8 [/SUP], Samaneh Delavari[SUP] 2 [/SUP], Paul Bastard[SUP] 7 8 [/SUP], Maribel Aranda-Guillén[SUP] 6 [/SUP], Yating Wang[SUP] 1 [/SUP], Fanglei Zuo[SUP] 1 [/SUP], Fabian Sardh[SUP] 5 6 [/SUP], Harold Marcotte[SUP] 9 [/SUP], Likun Du[SUP] 1 [/SUP], Shen-Ying Zhang[SUP] 4 [/SUP], Qian Zhang[SUP] 4 [/SUP], Nima Rezaei[SUP] 2 [/SUP], Olle Kämpe[SUP] 6 10 [/SUP], Jean-Laurent Casanova[SUP] 4 7 8 11 [/SUP], Lennart Hammarström[SUP] 1 [/SUP], Qiang Pan-Hammarström[SUP] 12 [/SUP]
Affiliations
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.
Keywords: ATM; COVID-19; TLR7; antibody deficiency; ataxia-telangiectasia; critical COVID-19; inborn errors of immunity; primary immunodeficiency.
. 2021 Oct 23;1-9.
doi: 10.1007/s10875-021-01151-y. Online ahead of print.
X-Linked TLR7 Deficiency Underlies Critical COVID-19 Pneumonia in a Male Patient with Ataxia-Telangiectasia
Hassan Abolhassani[SUP] 1 2 [/SUP], Ahmad Vosughimotlagh[SUP] 3 [/SUP], Takaki Asano[SUP] 4 [/SUP], Nils Landegren[SUP] 5 6 [/SUP], Bertrand Boisson[SUP] 4 7 8 [/SUP], Samaneh Delavari[SUP] 2 [/SUP], Paul Bastard[SUP] 7 8 [/SUP], Maribel Aranda-Guillén[SUP] 6 [/SUP], Yating Wang[SUP] 1 [/SUP], Fanglei Zuo[SUP] 1 [/SUP], Fabian Sardh[SUP] 5 6 [/SUP], Harold Marcotte[SUP] 9 [/SUP], Likun Du[SUP] 1 [/SUP], Shen-Ying Zhang[SUP] 4 [/SUP], Qian Zhang[SUP] 4 [/SUP], Nima Rezaei[SUP] 2 [/SUP], Olle Kämpe[SUP] 6 10 [/SUP], Jean-Laurent Casanova[SUP] 4 7 8 11 [/SUP], Lennart Hammarström[SUP] 1 [/SUP], Qiang Pan-Hammarström[SUP] 12 [/SUP]
Affiliations
- PMID: 34686943
- PMCID: PMC8536475
- DOI: 10.1007/s10875-021-01151-y
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.
Keywords: ATM; COVID-19; TLR7; antibody deficiency; ataxia-telangiectasia; critical COVID-19; inborn errors of immunity; primary immunodeficiency.