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000285456 1001_ $$aMoroncini, Gianluca$$b0
000285456 245__ $$aAdeno-associated virus type 5 infection via PDGFRα is associated with Interstitial lung disease in systemic sclerosis and generates composite peptides and epitopes recognized by the agonistic immunoglobulins present in patients with systemic sclerosis.
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000285456 500__ $$a2024 Apr;76(4):620-630
000285456 520__ $$aThe etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in SSc patients. Since PDGFRα is targeted of the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex.The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL). Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and Immunoaffinity-purified anti-PDGFRα antibodies from sera of SSc patients.AAV5 was detected in the BAL of 41 out of 66 (62.1%) SSc patients with interstitial lung disease and in 17 of 66 controls (25.75 %; p<0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from SSc patients, not from healthy controls.These data link AVV5 with the immune reactivity to endogenous antigens in SSc, and provide a novel element in the pathogenesis of SSc.
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000285456 7001_ $$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
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