9^th European Immunology Conference associated with Antibody Engineering Meeting

Psoriasis is a chronic infl ammatory and immune-mediated skin disease of unclear etiology, aff ecting 2-3% of individuals in Europe. A third of patients develop psoriatic arthritis (PsA), an infl ammatory arthritis associated with psoriasis. Th e exact mechanisms that lead to development of PsA in psoriasis patients are elusive. We previously uncovered that the antimicrobial peptide LL37, that is over-produced by keratinocytes in psoriasis skin, plays a crucial role in sustaining infl ammation in the skin by binding to nucleic acids and stimulating plasmacytoid and myeloid dendritic cells (pDC, mDCs) to release IFN-a and other pro-infl ammatory factors production. In psoriasis, LL37 also becomes the target of autoimmune T cells with a Th 1/ Th 17 phenotype. On the other hand, anti-LL37 antibodies are frequently detected in systemic lupus erythematosus, a systemic autoimmune disease characterized by increased neutrophil NETosis in target tissues. Furthermore, it is known that LL37 is the substrate for irreversible post-translational modifications (PTM), such as citrullination or carbamylation. In these work we showed the presence of native and modified LL37 and related anti-LL37 antibodies both in circulation and synovial fluids of psoriasis and PsA subjects as compared to healthy donors (HD) and osteoarthritis (OA) patients by ELISA. Moreover, we found the presence of inflammatory factors that can either recruit neutrophils and/or induce neutrophil activation/degranulation or NETosis, or citrullination of proteins (GM-CSF, C5a, IFN-a). In synovial biopsies from very early and untreated PsA patients, expression of the IFN-related gene MX1 is highly up-regulated in close proximity of myeloperoxidase and LL37 staining. Synovial anti-LL37 autoantibodies recognizing the citrullinated form of LL37 correlate with IFN-α expression, and both anticitrullinated and anti-carbamylated LL37 do correlate with GM-CSF. These results suggest that serum IFN-a, GM-CSF and anti-LL37 antibodies, especially those directed to carbamylated LL37 are potential disease markers in PsA.