AB0100 TO STUDY THE T CELL AND CYTOKINE PROFILE IN ANKYLOSING SPONDYLITIS WITH EFFECTS OF TACROLIMUS AND TADALAFIL ON THE CYTOKINES IN-VITRO

Background Most studies have shown mixed results of Interleukin (IL)17 and IL-23 levels in patients with Ankylosing Spondylitis (AS) compared to controls; animal showing a good correlation between activation IL 23-IL 27 pathway radiologic progression. Targeting this humans has yielded benefits reduced inflammation progression AS. Controlling fibrosis is the key prevent osteoproliferation. Tacrolimus tadalafil inhibit Th17 profibrotic pathways respectively. Objectives To study T cell (Th17, PD1, CD25+ CD4 cells) cytokine profile (IL-17, IL-23, TGF- β) AS influence disease duration activity on above profile. also effect tacrolimus ex-vivo peripheral blood monocyte (PBMC) cultures their anti-inflammatory anti-fibrotic potential. Methods Patients (ASAS classification criteria) without not biologic therapy were recruited demographic, clinical profile, indices recorded. Age sex matched healthy controls (HC, n=21) recruited. Peripheral was drawn sera stored; PBMCs isolated cultured. Serum PBMC culture supernatant (CS) measured for IL-17, TGF-β. These cytokines at baseline, after stimulation anti-CD3CD28 antibodies, treatment tacrolimus(10mM/ml), tadalafil(10mM/ml) both drugs combined by ELISA(R&D systems, USA). The characterized flow cytometry (CD4 Th17, PD1 CD25). Statistical analysis done using GraphPad prism v9. Results Twenty-five [28(24-36),M:F, 7.3:1] enrolled 90% HLA-B27 positivity. majority had moderate-high as per ASDAS CRP NSAIDs(24), complementary medications (7) two each methotrexate sulfasalazine. IL-17 TGF-β, CS β significantly elevated controls. All measures populations HC. When stratified disease, parameters, indices, T-cell similar across groups. showed significant CD4Th17+ cells (r=0.7, p=0.009) PD1/T reg (r=-0.6, p=0.03). A positive association observed some but generalized linear modeling (Table 1). No or profiling Modified Stokes Score. There decline combined, however, no such difference IL-23. (Figure 1) Conclusion early late disease. seen tadalafil. This needs further exploration larger sample size subgroup characterization well testing synovial fluid joint tissue samples. Table 1. Association cell/cytokine Multivariate GLM OR (95%CI) Model 1 CD4+Th17 1.4(0.6-2.2) 0.003** CD4+PD1+ -0.3(-0.7-0.1) 0.07 PD1+Th17 -0.1(-0.12-0.01) 0.1 2 CD4+Th17/CD25+ 3.5(0.7-6.3) 0.02* CD4+PD1+/CD25+ -0.2(0.4- -0.02) 0.03* PD1+Th17/CD25+ -0.6(-2.3-1.1) 0.5 3 -0.01(-0.05-0.03) -0.01(-0.1-0.08) 0.8 TGF-β -0.00(-0.001-6.7) Figure In vitro CD3 CD28 stimulation, addition tacrolimus, its combination. REFERENCES: NIL. Acknowledgements: Disclosure Interests None Declared.