Pulmonary Alveolar Proteinosis and Multiple Infectious Diseases in a Child with Autosomal Recessive Complete IRF8 Deficiency - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Immunology Année : 2022

Pulmonary Alveolar Proteinosis and Multiple Infectious Diseases in a Child with Autosomal Recessive Complete IRF8 Deficiency

Jérémie Rosain
Andrea Bernasconi
  • Fonction : Auteur
Emma Prieto
  • Fonction : Auteur
Lucia Caputi
  • Fonction : Auteur
Tom Le Voyer
Guadalupe Buda
  • Fonction : Auteur
Marcelo Marti
  • Fonction : Auteur
Jonathan Bohlen
Anna-Lena Neehus
Claudio Castaños
  • Fonction : Auteur
Rosario Gallagher
  • Fonction : Auteur
Matias Oleastro
  • Fonction : Auteur
Laura Perez
  • Fonction : Auteur
Silvia Danielian
  • Fonction : Auteur
Jose Edgardo Dipierri
  • Fonction : Auteur
Jean-Laurent Casanova
Jacinta Bustamante
Mariana Villa
  • Fonction : Auteur

Résumé

Abstract Background Autosomal recessive (AR) complete IRF8 deficiency is a rare severe inborn error of immunity underlying an absence of blood myeloid mononuclear cells, intracerebral calcifications, and multiple infections. Only three unrelated patients have been reported. Materials and Methods We studied an Argentinian child with multiple infectious diseases and severe pulmonary alveolar proteinosis (PAP). We performed whole-exome sequencing (WES) and characterized his condition by genetic, immunological, and clinical means. Results The patient was born and lived in Argentina. He had a history of viral pulmonary diseases, disseminated disease due to bacillus Calmette-Guérin (BCG), PAP, and cerebral calcifications. He died at the age of 10 months from refractory PAP. WES identified two compound heterozygous variants in IRF8 : c.55del and p.R111*. In an overexpression system, the p.R111* cDNA was loss-of-expression, whereas the c.55del cDNA yielded a protein with a slightly lower molecular weight than the wild-type protein. The mutagenesis of methionine residues downstream from c.55del revealed a re-initiation of translation. However, both variants were loss-of-function in a luciferase assay, suggesting that the patient had AR complete IRF8 deficiency. The patient had no blood monocytes or dendritic cells, associated with neutrophilia, and normal counts of NK and other lymphoid cell subsets. Conclusion We describe the fourth patient with AR complete IRF8 deficiency. This diagnosis should be considered in children with PAP, which is probably due to the defective development or function of alveolar macrophages.

Dates et versions

hal-03989473 , version 1 (14-02-2023)

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Citer

Jérémie Rosain, Andrea Bernasconi, Emma Prieto, Lucia Caputi, Tom Le Voyer, et al.. Pulmonary Alveolar Proteinosis and Multiple Infectious Diseases in a Child with Autosomal Recessive Complete IRF8 Deficiency. Journal of Clinical Immunology, 2022, 42 (5), pp.975-985. ⟨10.1007/s10875-022-01250-4⟩. ⟨hal-03989473⟩
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