Heterozygous Predicted Loss-of-function Variants of TRAF3 in Patients with Common Variable Immunodeficiency.

Autor: Urban B; Translational Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain., Batlle-Masó L; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Infection and Immunity in Pediatric Patient, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Pediatric Infectious Diseases and Immunodeficiencies Unit, Children's Hospital, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain., Perurena-Prieto J; Translational Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Bellaterra, Catalonia, Spain., Garcia-Prat M; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Infection and Immunity in Pediatric Patient, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Pediatric Infectious Diseases and Immunodeficiencies Unit, Children's Hospital, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain., Parra-Martínez A; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Infection and Immunity in Pediatric Patient, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Pediatric Infectious Diseases and Immunodeficiencies Unit, Children's Hospital, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain., Aguiló-Cucurull A; Translational Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain., Martinez-Gallo M; Translational Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Bellaterra, Catalonia, Spain., Moushib L; Translational Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Bellaterra, Catalonia, Spain., Antolín M; Department of Clinical and Molecular Genetics, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Medicine Genetics Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain., Rivière JG; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Infection and Immunity in Pediatric Patient, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Pediatric Infectious Diseases and Immunodeficiencies Unit, Children's Hospital, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain., Soler-Palacin P; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain.; Infection and Immunity in Pediatric Patient, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Pediatric Infectious Diseases and Immunodeficiencies Unit, Children's Hospital, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain., Dieli-Crimi R; Translational Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain.; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain., Franco-Jarava C; Immunology Department, Laboratori Clinic ICS Camp de Tarragona, Hospital Joan XXIII, Tarragona, Catalonia, Spain. clfranco.hj23.ics@gencat.cat., Colobran R; Translational Immunology Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain. roger.colobran@vallhebron.cat.; Immunology Division, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain. roger.colobran@vallhebron.cat.; Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain. roger.colobran@vallhebron.cat.; Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB), Bellaterra, Catalonia, Spain. roger.colobran@vallhebron.cat.; Department of Clinical and Molecular Genetics, Hospital Universitari Vall d'Hebron (HUVH), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain. roger.colobran@vallhebron.cat.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2024 Nov 23; Vol. 45 (1), pp. 47. Date of Electronic Publication: 2024 Nov 23.
DOI: 10.1007/s10875-024-01833-3
Abstrakt: TRAF3, a versatile adaptor protein within the TRAF family, participates in various signaling pathways involving the tumor necrosis factor receptor, toll-like receptor, and retinoic acid-inducible gene I-like receptor families. In 2010, autosomal dominant TRAF3 deficiency was reported in a patient with herpes simplex virus-1 encephalitis, consistent with the role of TRAF3 in type I interferon production. Recently, a novel, completely different clinical phenotype was described in patients with TRAF3 haploinsufficiency (TRAF3 Hl ), characterized by recurrent bacterial infections, autoimmune features, systemic inflammation, and hypergammaglobulinemia. In this study, we conducted a TRAF3-targeted reanalysis of next-generation sequencing data from 800 patients with inborn errors of immunity. Through this reassessment and additional familial investigations, we identified three previously unidentified cases of TRAF3 Hl within two different families. These individuals harbored stop-gain variants (p.Arg163* and p.Gln407*) and experienced recurrent bacterial infections with hypogammaglobulinemia. Previously, the patients had been diagnosed with common variable immunodeficiency (CVID) and were receiving immunoglobulin replacement therapy. In addition, a TRAF3 start-loss variant (c.3G > A) was identified in a fourth patient, but after familial and molecular studies, it was not considered disease-causing, excluding TRAF3 Hl in this patient. This study illustrates the usefulness of targeted reanalysis of genes with reported novel phenotypes. We rescued three patients with TRAF3 Hl , presenting similarities and differences with the previously reported patients. The most significant differences were hypogammaglobulinemia and a CVID-like presentation. These data expand the clinical phenotype of TRAF3 Hl and pave the way for further investigation into loss-of-function variants in patients with CVID.
Competing Interests: Declarations. Ethical Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Vall d’Hebron University Hospital: date: 11/06/2021, code: PR(AG)202/2021. Consent to Participate: Informed consent was obtained from all individuals participating in the study. Consent to Publish: The authors affirm that the human research participants provided informed consent for publication of the data in this manuscript. Competing Interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: