| Title: |
Neutralizing IFN-γ autoantibodies are rare and pathogenic in HLA-DRB1*15:02 or 16:02 individuals |
| Authors: |
Peel, Jessica, N; Yang, Rui; Le Voyer, Tom; Gervais, Adrian; Rosain, Jérémie; Bastard, Paul; Behere, Anish; Cederholm, Axel; Bodansky, Aaron; Seeleuthner, Yoann; Conil, Clément; Ding, Jing-Ya; Lei, Wei-Te; Bizien, Lucy; Soudee, Camille; Migaud, Mélanie; Ogishi, Masato; Yatim, Ahmad; Lee, Danyel; Bohlen, Jonathan; Perpoint, Thomas; Perez, Laura; Messina, Fernando; Genet, Roxana; Karkowski, Ludovic; Blot, Mathieu; Lafont, Emmanuel; Toullec, Laurie; Goulvestre, Claire; Mehlal-Sedkaoui, Souad; Sallette, Jérôme; Martin, Fernando; Puel, Anne; Jouanguy, Emmanuelle; Anderson, Mark, S; Landegren, Nils; Tiberghien, Pierre; Abel, Laurent; Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; Ku, Cheng-Lung; Casanova, Jean-Laurent |
| Contributors: |
St. Giles Laboratory of Human Genetics of Infectious Diseases; Rockefeller University New York; Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Hopital Saint-Louis AP-HP (AP-HP); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Hôpital Necker - Enfants Malades AP-HP; Uppsala University; University of California San Francisco (UC San Francisco); University of California (UC); Chang Gung University Taïwan; Hsinchu Cathay General Hospital (CGH); Hospices Civils de Lyon (HCL); Hospital Nacional de Pediatría Garrahan - Garrahan National Paediatric Hospital; Hospital Francisco Javier Muñiz; Centre hospitalier régional de Metz-Thionville (CHR Metz-Thionville); Hopital d'instruction des armées Sainte-Anne Toulon (HIA); Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); Université Paris Cité (UPCité); Hôpital Cochin AP-HP; Laboratoire CERBA Saint Ouen l'Aumône; Karolinska Institutet = Karolinska Institute Stockholm; Établissement Français du Sang La Plaine Saint-Denis (EFS); Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT); Institut National de la Santé et de la Recherche Médicale (INSERM)-Établissement Français du Sang Bourgogne-Franche-Comté Besançon (EFS BFC - Besançon); Établissement Français du Sang La Plaine Saint-Denis (EFS)-Établissement Français du Sang La Plaine Saint-Denis (EFS)-Université de Franche-Comté (UFC); Université Bourgogne Franche-Comté COMUE (UBFC)-Université Bourgogne Franche-Comté COMUE (UBFC); Chang Gung Memorial Hospital Taipei (CGMH); Howard Hughes Medical Institute Boston (HHMI); Howard Hughes Medical Institute (HHMI)-Harvard Medical School Boston (HMS); ANR-22-CE92-0008,MAFMACRO,Genetic predisposition and the role of myeloid cells in the susceptibility to mycobacterial infection(2022); ANR-22-CE15-0046,AI2D,Autoanticorps anti-interférons et maladies infectieuses associées(2022); ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020); ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021) |
| Source: |
ISSN: 1558-8238 ; The Journal of clinical investigation ; https://hal.science/hal-04815928 ; The Journal of clinical investigation, 2024, 134 (8), pp.e178263. ⟨10.1172/JCI178263⟩. |
| Publisher Information: |
CCSD; American Society for Clinical Investigation |
| Publication Year: |
2024 |
| Subject Terms: |
Autoimmune diseases; Cytokines; Genetics; Immunology; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; BACKGROUND. Weakly virulent environmental mycobacteria (EM) can cause severe disease in HLA-DRB1*15:02 or 16:02 adults harboring neutralizing anti-IFN-γ autoantibodies (nAIGAs). The overall prevalence of nAIGAs in the general population is unknown, as are the penetrance of nAIGAs in HLA-DRB1*15:02 or 16:02 individuals and the proportion of patients with unexplained, adult-onset EM infections carrying nAIGAs. METHODS. This study analyzed the detection and neutralization of anti-IFN-γ autoantibodies (auto-Abs) from 8,430 healthy individuals of the general population, 257 HLA-DRB1*15:02 or 16:02 carriers, 1,063 patients with autoimmune disease, and 497 patients with unexplained severe disease due to EM. RESULTS. We found that anti-IFN-γ auto-Abs detected in 4,148 of 8,430 healthy individuals (49.2%) from the general population of an unknown HLA-DRB1 genotype were not neutralizing. Moreover, we did not find nAIGAs in 257 individuals carrying HLA-DRB1* 15:02 or 16:02. Additionally, nAIGAs were absent in 1,063 patients with an autoimmune disease. Finally, 7 of 497 patients (1.4%) with unexplained severe disease due to EM harbored nAIGAs. CONCLUSION. These findings suggest that nAIGAs are isolated and that their penetrance in HLA-DRB1*15:02 or 16:02 individuals is low, implying that they may be triggered by rare germline or somatic variants. In contrast, the risk of mycobacterial disease in patients with nAIGAs is high, confirming that these nAIGAs are the cause of EM disease. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38470480; PUBMED: 38470480; PUBMEDCENTRAL: PMC11014650 |
| DOI: |
10.1172/JCI178263 |
| Availability: |
https://hal.science/hal-04815928; https://hal.science/hal-04815928v1/document; https://hal.science/hal-04815928v1/file/jci-134-178263.pdf; https://doi.org/10.1172/JCI178263 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.2DE78F6F |
| Database: |
BASE |