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

dc.rights.licenseopenen_US
dc.contributor.authorHARTL, J.
dc.contributor.authorSERPAS, L.
dc.contributor.authorWANG, Y.
dc.contributor.authorRASHIDFARROKHI, A.
dc.contributor.authorPEREZ, O.A.
dc.contributor.authorSALLY, B.
hal.structure.identifierImmunology from Concept and Experiments to Translation [ImmunoConcept]
dc.contributor.authorSISIRAK, Vanja
dc.contributor.authorSONI, C.
dc.contributor.authorKHODADADI-JAMAYRAN, A.
dc.contributor.authorTSIRIGOS, A.
dc.contributor.authorCAIELLO, I.
dc.contributor.authorBRACAGLIA, C.
dc.contributor.authorVOLPI, S.
dc.contributor.authorGHIGGERI, G.M.
dc.contributor.authorCHIDA, A.S.
dc.contributor.authorSANZ, I.
dc.contributor.authorKIM, M.Y.
dc.contributor.authorMICHAEL BELMONT, H.
dc.contributor.authorSILVERMAN, G.J.
dc.contributor.authorCLANCY, R.M.
dc.contributor.authorIZMIRLY, P.M.
dc.contributor.authorBUYON, J.P.
dc.contributor.authorREIZIS, B.
dc.date.accessioned2022-05-04T07:40:10Z
dc.date.available2022-05-04T07:40:10Z
dc.date.issued2021-05-03
dc.identifier.issn1540-9538 (online) 0022-1007 (print)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/139975
dc.description.abstractEnAntibodies 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.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.title.enAutoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus
dc.typeArticle de revueen_US
dc.identifier.doi10.1084/jem.20201138en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
bordeaux.journalJournal of Experimental Medicineen_US
bordeaux.volume218en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDLupus Research Allianceen_US
bordeaux.identifier.funderIDDeutsche Forschungsgemeinschaften_US
bordeaux.identifier.funderIDColton Foundationen_US
hal.exportfalse
dc.rights.ccCC BY-NC-SAen_US
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