HARTL, J.; SERPAS, L.; WANG, Y.; RASHIDFARROKHI, A.; PEREZ, O.A.; SALLY, B.; SISIRAK, Vanja; SONI, C.; KHODADADI-JAMAYRAN, A.; TSIRIGOS, A.; CAIELLO, I.; BRACAGLIA, C.; VOLPI, S.; GHIGGERI, G.M.; CHIDA, A.S.; SANZ, I.; KIM, M.Y.; MICHAEL BELMONT, H.; SILVERMAN, G.J.; CLANCY, R.M.; IZMIRLY, P.M.; BUYON, J.P.; REIZIS, B.

doi:10.1084/jem.20201138

Langue

Article de revue

Ce document a été publié dans

Journal of Experimental Medicine. 2021-05-03, vol. 218, n° 5

Résumé en anglais

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >50% of sporadic SLE patients with nephritis manifested reduced DNASE1L3 activity in circulation, which was associated with neutralizing autoantibodies to DNASE1L3. These patients had normal total plasma cfDNA levels but showed accumulation of cfDNA in circulating microparticles. Microparticle-associated cfDNA contained a higher fraction of longer polynucleosomal cfDNA fragments, which bound autoantibodies with higher affinity than mononucleosomal fragments. Autoantibodies to DNASE1L3- sensitive antigens on microparticles were prevalent in SLE nephritis patients and correlated with the accumulation of cfDNA in microparticles and with disease severity. DNASE1L3-sensitive antigens included DNA-associated proteins such as HMGB1. Our results reveal autoantibody-mediated impairment of DNASE1L3 activity as a common nongenetic mechanism facilitating antidsDNA autoreactivity in patients with severe sporadic SLE.< Réduire

URI

https://oskar-bordeaux.fr/handle/20.500.12278/139975

DOI

http://dx.doi.org/10.1084/jem.20201138

Unités de recherche

ImmunoConcEpT - UMR 5164

Voir/Ouvrir

Métadonnées

Partager cette publication !

Licence d’utilisation du document

Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus

Langue

Ce document a été publié dans

Résumé en anglais

URI

DOI

Unités de recherche