000285456 001__ 285456 000285456 005__ 20240328133525.0 000285456 0247_ $$2doi$$a10.1002/art.42746 000285456 0247_ $$2pmid$$apmid:37975161 000285456 0247_ $$2ISSN$$a2326-5191 000285456 0247_ $$2ISSN$$a0004-3591 000285456 0247_ $$2ISSN$$a0893-7524 000285456 0247_ $$2ISSN$$a1529-0123 000285456 0247_ $$2ISSN$$a1529-0131 000285456 0247_ $$2ISSN$$a2326-5205 000285456 0247_ $$2altmetric$$aaltmetric:156575004 000285456 037__ $$aDKFZ-2023-02390 000285456 041__ $$aEnglish 000285456 082__ $$a610 000285456 1001_ $$aMoroncini, Gianluca$$b0 000285456 245__ $$aAdeno-associated virus type 5 infection via PDGFRα is associated with Interstitial lung disease in systemic sclerosis and generates composite peptides and epitopes recognized by the agonistic immunoglobulins present in patients with systemic sclerosis. 000285456 260__ $$aHoboken, NJ$$bWiley$$c2024 000285456 3367_ $$2DRIVER$$aarticle 000285456 3367_ $$2DataCite$$aOutput Types/Journal article 000285456 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1711629278_3151 000285456 3367_ $$2BibTeX$$aARTICLE 000285456 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000285456 3367_ $$00$$2EndNote$$aJournal Article 000285456 500__ $$a2024 Apr;76(4):620-630 000285456 520__ $$aThe etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in SSc patients. Since PDGFRα is targeted of the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex.The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL). Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and Immunoaffinity-purified anti-PDGFRα antibodies from sera of SSc patients.AAV5 was detected in the BAL of 41 out of 66 (62.1%) SSc patients with interstitial lung disease and in 17 of 66 controls (25.75 %; p<0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from SSc patients, not from healthy controls.These data link AVV5 with the immune reactivity to endogenous antigens in SSc, and provide a novel element in the pathogenesis of SSc. 000285456 536__ $$0G:(DE-HGF)POF4-316$$a316 - Infektionen, Entzündung und Krebs (POF4-316)$$cPOF4-316$$fPOF IV$$x0 000285456 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000285456 7001_ $$aSvegliati, Silvia$$b1 000285456 7001_ $$aGrieco, Antonella$$b2 000285456 7001_ $$aCuccioloni, Massimiliano$$b3 000285456 7001_ $$aMozzicafreddo, Matteo$$b4 000285456 7001_ $$aPaolini, Chiara$$b5 000285456 7001_ $$aAgarbati, Silvia$$b6 000285456 7001_ $$aSpadoni, Tatiana$$b7 000285456 7001_ $$aAmoresano, Angela$$b8 000285456 7001_ $$aPinto, Gabriella$$b9 000285456 7001_ $$0P:(DE-He78)22044c593297ed69ad001df11dd0d669$$aChen, Qingxin$$b10 000285456 7001_ $$aBenfaremo, Devis$$b11 000285456 7001_ $$aTonnini, Cecilia$$b12 000285456 7001_ $$aSenzacqua, Martina$$b13 000285456 7001_ $$aAlizzi, Silvia$$b14 000285456 7001_ $$0P:(DE-HGF)0$$aNieto, Karen$$b15 000285456 7001_ $$aFinke, Doreen$$b16 000285456 7001_ $$aViola, Nadia$$b17 000285456 7001_ $$aAmico, Donatella$$b18 000285456 7001_ $$aGalgani, Mario$$b19 000285456 7001_ $$aGasparini, Stefano$$b20 000285456 7001_ $$aZuccatosta, Lina$$b21 000285456 7001_ $$aMenzo, Stefano$$b22 000285456 7001_ $$0P:(DE-He78)47d2c5b8ee00ab8a0c16e14137427579$$aMüller, Martin$$b23$$udkfz 000285456 7001_ $$0P:(DE-HGF)0$$aKleinschmidt, Juergen$$b24 000285456 7001_ $$aFunaro, Ada$$b25 000285456 7001_ $$aGiordano, Antonio$$b26 000285456 7001_ $$00000-0002-8839-0933$$aLa Cava, Antonio$$b27 000285456 7001_ $$aDorfmuller, Peter$$b28 000285456 7001_ $$aAmoroso, Antonio$$b29 000285456 7001_ $$aPucci, Piero$$b30 000285456 7001_ $$00000-0002-0068-6212$$aPezone, Antonio$$b31 000285456 7001_ $$aAvvedimento, Enrico V$$b32 000285456 7001_ $$00000-0003-3189-5516$$aGabrielli, Armando$$b33 000285456 773__ $$0PERI:(DE-600)2754614-7$$a10.1002/art.42746$$gp. art.42746$$n4$$p620-630$$tArthritis & rheumatology$$v76$$x2326-5191$$y2024 000285456 909CO $$ooai:inrepo02.dkfz.de:285456$$pVDB 000285456 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)22044c593297ed69ad001df11dd0d669$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ 000285456 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b15$$kDKFZ 000285456 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)47d2c5b8ee00ab8a0c16e14137427579$$aDeutsches Krebsforschungszentrum$$b23$$kDKFZ 000285456 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b24$$kDKFZ 000285456 9131_ $$0G:(DE-HGF)POF4-316$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vInfektionen, Entzündung und Krebs$$x0 000285456 9141_ $$y2023 000285456 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2023-10-26$$wger 000285456 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bARTHRITIS RHEUMATOL : 2022$$d2023-10-26 000285456 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bARTHRITIS RHEUMATOL : 2022$$d2023-10-26 000285456 9201_ $$0I:(DE-He78)F035-20160331$$kF035$$lTumorvirus-spez. 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