{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T01:00:39Z","timestamp":1759971639671,"version":"build-2065373602"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet\u2010derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFR\u03b1 is targeted by the adeno\u2010associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFR\u03b1 exposing epitopes that may induce the immune responses to the virus\u2013PDGFR\u03b1 complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The binding of monomeric human PDGFR\u03b1 to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFR\u03b1 locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFR\u03b1 were evaluated by SPR using SSc monoclonal anti\u2010PDGFR\u03b1 antibodies and immunoaffinity\u2010purified anti\u2010PDGFR\u03b1 antibodies from sera of patients with SSc.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (<jats:italic>P<\/jats:italic> &lt;\u20090.001). In SSc lungs, AAV5 localized\u2009in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFR\u03b1 was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti\u2010PDGFR\u03b1 antibodies identified spatially contiguous epitopes derived from PDGFR\u03b1 and AAV5 that interacted with SSc agonistic antibodies to PDGFR\u03b1. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42746-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42746","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T03:37:29Z","timestamp":1700192249000},"page":"620-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adeno\u2010Associated Virus Type 5 Infection via <scp>PDGFR\u03b1<\/scp> 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"],"prefix":"10.1002","volume":"76","author":[{"given":"Gianluca","family":"Moroncini","sequence":"first","affiliation":[{"name":"Universit\u00e0 Politecnica delle Marche and Azienda Ospedaliero Universitaria delle Marche  Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Svegliati","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Politecnica delle Marche  Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Grieco","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Politecnica delle Marche  Ancona 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