TY - JOUR AU - Moroncini, Gianluca AU - Svegliati, Silvia AU - Grieco, Antonella AU - Cuccioloni, Massimiliano AU - Mozzicafreddo, Matteo AU - Paolini, Chiara AU - Agarbati, Silvia AU - Spadoni, Tatiana AU - Amoresano, Angela AU - Pinto, Gabriella AU - Chen, Qingxin AU - Benfaremo, Devis AU - Tonnini, Cecilia AU - Senzacqua, Martina AU - Alizzi, Silvia AU - Nieto, Karen AU - Finke, Doreen AU - Viola, Nadia AU - Amico, Donatella AU - Galgani, Mario AU - Gasparini, Stefano AU - Zuccatosta, Lina AU - Menzo, Stefano AU - Müller, Martin AU - Kleinschmidt, Juergen AU - Funaro, Ada AU - Giordano, Antonio AU - La Cava, Antonio AU - Dorfmuller, Peter AU - Amoroso, Antonio AU - Pucci, Piero AU - Pezone, Antonio AU - Avvedimento, Enrico V AU - Gabrielli, Armando TI - Adeno-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. JO - Arthritis & rheumatology VL - 76 IS - 4 SN - 2326-5191 CY - Hoboken, NJ PB - Wiley M1 - DKFZ-2023-02390 SP - 620-630 PY - 2024 N1 - 2024 Apr;76(4):620-630 AB - 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 LB - PUB:(DE-HGF)16 C6 - pmid:37975161 DO - DOI:10.1002/art.42746 UR - https://inrepo02.dkfz.de/record/285456 ER -