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- W2910824478 abstract "Background The antimicrobial peptide LL37 plays a pathogenic role in psoriasis (Pso) due to its adjuvant and auto-antigenic properties. At least a third of Pso patients develop psoriatic arthritis (PsA) but mechanisms that lead PsA development in Pso patients remain elusive. Objectives To understand the role of LL37 in PsA pathogenesis and its relationship with inflammatory molecules IFNa, GMCSF, C5a. Methods Blood samples were collected from 32 biologic-naive PsA, 12 active Pso (without PsA) patients and 8 healthy donors (HD). Synovial fluids (SF) were collected from 17 PsA and 12 osteohartritis (OA) patients. Synovial biopsies from 3 biologic-naive PsA patients were studied by confocal microscopy. Native-LL37 was synthesised and carbamylated LL37 (LL37carb) produced by incubating LL37 with 1 M potassium cyanate and verified by dot-blot assay. Antibodies to native-LL37/LL37carb and levels of LL37, GMCSF, IFNa and complement C5a were measured by in-house and commercial ELISA tests, respectively, in SF and plasma. Results High LL37 levels were detectable in SF of PsA compared to OA. Anti-LL37 [24% in SF (4/17)] and anti-LL37carb antibodies [47% in SF (8/17), 46% in plasma (15/32)] were present in PsA but not in OA and HD. Anti-LL37carb antibodies [41% (5/12)] were also detectable in Pso plasma. IFNa was present in 37% of SF PsA (7/16; not detectable in OA) and correlated with C-reactive Protein (CRP); GMCSF and C5a levels were significantly higher in SF PsA than in SF OA. Notably, GMCSF was also detectable in 40% and 30% of PsA and Pso plasma, respectively, but not in HD; Plasma C5a levels were comparable between PsA and Pso and significantly higher than in HD. SF GMCSF correlated with anti-LL37carb autoantibodies. Anti-LL37carb antibodies correlated with levels of C5a in Pso and PsA plasma. In synovial tissues of PsA the expression of the IFN-related gene MX1 was highly up-regulated in close proximity of neutrophil markers myeloperoxidase and LL37. Conclusions LL37 and, in particular, LL37carb is the target of autoantibodies that correlate with pro-inflammatory GMCSF and C5a in both Pso and PsA, suggesting immunological pathways in common between psoriasis and psoriatic arthritis. Reference ] Lande R, et al. Nature 2007;449:564. ] Lande R, et al. Sci Transl Med 2011;3(73):73ra19. [] Lande R, et al. Nat Commun2014;5:5621. [] Chimenti MS, et al. Autoimmun Rev2015;14(12):1142. Disclosure of Interest None declared" @default.
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- W2910824478 date "2018-06-01" @default.
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- W2910824478 title "SAT0039 Ll37 up-regulation and anti-ll37 reactivity are shared by psoriasis and psoriatic arthritis patients" @default.
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