Fiche publication
Date publication
janvier 2024
Journal
Genes and immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak
,
Dr CARAPITO Raphaël
,
Pr MARTIN Thierry
Tous les auteurs :
Guffroy A, Jacquel L, Seeleuthner Y, Paul N, Poindron V, Maurier F, Delannoy V, Voegeli AC, Zhang P, Nespola B, Molitor A, Apithy MJ, Soulas-Sprauel P, Martin T, Voll RE, Bahram S, Gies V, Casanova JL, Cobat A, Boisson B, Carapito R, Korganow AS
Lien Pubmed
Résumé
Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown. We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti β2 glycoprotein1 autoantibodies. We performed whole exome sequencing. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort. We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity. These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous series of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.
Référence
Genes Immun. 2024 01 24;:
