% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Moroncini:285456, author = {G. Moroncini and S. Svegliati and A. Grieco and M. Cuccioloni and M. Mozzicafreddo and C. Paolini and S. Agarbati and T. Spadoni and A. Amoresano and G. Pinto and Q. Chen$^*$ and D. Benfaremo and C. Tonnini and M. Senzacqua and S. Alizzi and K. Nieto$^*$ and D. Finke and N. Viola and D. Amico and M. Galgani and S. Gasparini and L. Zuccatosta and S. Menzo and M. Müller$^*$ and J. Kleinschmidt$^*$ and A. Funaro and A. Giordano and A. La Cava and P. Dorfmuller and A. Amoroso and P. Pucci and A. Pezone and E. V. Avvedimento and A. Gabrielli}, title = {{A}deno-associated virus type 5 infection via {PDGFR}α is associated with {I}nterstitial lung disease in systemic sclerosis and generates composite peptides and epitopes recognized by the agonistic immunoglobulins present in patients with systemic sclerosis.}, journal = {Arthritis $\&$ rheumatology}, volume = {76}, number = {4}, issn = {2326-5191}, address = {Hoboken, NJ}, publisher = {Wiley}, reportid = {DKFZ-2023-02390}, pages = {620-630}, year = {2024}, note = {2024 Apr;76(4):620-630}, abstract = {The 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.}, cin = {F035}, ddc = {610}, cid = {I:(DE-He78)F035-20160331}, pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)}, pid = {G:(DE-HGF)POF4-316}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:37975161}, doi = {10.1002/art.42746}, url = {https://inrepo02.dkfz.de/record/285456}, }