OP0054 NEW ROLE FOR PROTEINASE 3 IN IL-16 BIOACTIVITY CONTROL IN GRANULOMATOSIS WITH POLYANGIITIS

Background: The immunomodulatory cytokine IL-16 is increased in several inflammatory and autoimmune diseases 1 . recruits activates CD4+ immune cells such as T cells, dendritic or monocytes. produced by various non-immune but synthesis storage of regulated differentially depending on the cell type stimulation. For its biological activity, cleavage caspase-3 required Necrotizing granulomatous inflammation a hallmark granulomatosis with polyangiitis (GPA) neutrophil dysregulation central driver chronic autoimmunity 2 Earlier studies showed correlation between serum disease parameters AAV, including GPA 3 , functional evidence for direct link neutrophils missing so far. Objectives: In this study we aim to identify IL-16, neutrophils, autoantigen proteinase (PR3) regard GPA. Methods: was measured sera patients (n = 40) healthy controls (HC, n 50) ELISA correlated clinical features, activity (BVAS), creatinine, GFR, VDI PR3-ANCA status. protein expression analyzed peripheral blood mononuclear (PBMC) polymorphonuclear (PMN) from HC 5, each) SDS-PAGE western blot. Binding affinity recombinant pro-IL-16 native human PR3 assessed microscale thermophoresis. Cleavage active performed at time points 37°C. products were Results: Circulating significantly compared HC. Elevated positively BVAS, status negatively GFR. PMBC PMN identified different patters precursor forms IL-16. PBMC found high amounts (80kD), (55kD) (17kD). contrast, had lower no indicating activation secretion due stimulation, shown earlier 5 detected form, contrast very low all PMN. Processing release has been linked apoptosis secondary necrosis By interaction demonstrated binding Kd 10 nM. subsequent assay confirmed processing time-dependent manner. Conclusion: Correlation features suggests that associated markers tissue damage autoreactivity. We represent source identification an additional IL-16-activating enzyme could demonstrate potential excessive expression, death IL-16-dependent mechanisms, contributing References: [1]Glass, W. G. et al. Not-so-sweet sixteen: role infectious immune-mediated diseases. J. Interf. Cytokine Res. 26, 511–520 (2006). [2]Millet, A. Proteinase apoptotic disrupts silencing vasculitis. Clin. Invest. 125, 4107–4121 (2015). [3]Yoon, T. Serum interleukin-16 correlates Vasculitis Damage Index antineutrophil cytoplasmic antibody-associated Arthritis Ther. 22, 1–6 (2020). [4]Elssner, Is Constitutively Present Peripheral Blood Monocytes Spontaneously Released During Apoptosis. Immunol. 172, 7721–7725 (2004). [5]Roth, S. Secondary necrotic interleukin-16C macrophage migration inhibitory factor stores cytosol. Cell Death Discov. 1, 15056 Disclosure Interests: None declared