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@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},
}