A MULTIOMICS PLASMA ANALYSIS REVEALS NEW PATHWAYS CENTRAL IN DRIVING INFLAMMATION IN SPONDYLOARTHRITIS

S. R. Greisen, R. Østgård, S. E. Rask, M. Hvid, A. G. Jurik, U. Syrbe, D. Poddubnyy, B. DeleuranAarhus Univeristy, Biomedicine, Aarhus, Denmark Aarhus University Hospital, Rheumatology, Aarhus, Denmark Silkeborg Regional Hospital, Rheumatology, Silkeborg, Denmark Aarhus University, Clinical Medicine, Aarhus, Denmark Aarhus University Hospital, Radiology, Aarhus, Denmark Charité Universitätsmedizin Berlin, Gastroenterology, Infectiology and Rheumatology, Berlin, Germany  Background Biochemical and clinical disease activity markers in spondyloarthritis (SpA) remain scarce. In addition, understanding the pathways driving disease progression with a combination of bone formation and bone erosions still remain to be fully elucidated. Anti-TNF-α and anti-IL-17A treatment decrease clinical symptoms and partly limit structural changes, but still disease progression and treatment failure occur. Objectives We used an unbiased multiomics plasma analysis to identify inflammatory proteins associated with disease activity and structural changes. Subsequently, some of the identified proteins were investigated in biopsies from the spine and in cells, and synovial fluid from the peripheral joint. Methods Blood was obtained from patients with early (eSpA) before and 1 year after start of anti-TNF treatment (n=30). Markers of disease activity included; BASDAI, ASDAS, CRP. Osteitis, bone marrow edema and new bone formation were evaluated by MRI scan of the total spine and the SI-joint at baseline and after 1 year of treatment. Healthy controls (HCs) were age and gender matched (n=15). From patients with long-standing SpA (lsSpA, symptom duration >8 years) with a joint effusion, both blood (n= 8) and synovial fluid (SF) (n=6) was obtained. An O-link based multipanel analysis covering 92 proteins was performed on plasma and synovial fluid. Cells were stained for flow. Facet joint biopsies originated from lsSpA patients undergoing surgery for polysegmental correction of rigid hyperkyphosis. These were stained by immune fluorescence. P < 0.05 was accepted as significant. Results The multiomics analysis revealed 18 proteins significantly increased at baseline compared to after one year of anti-TNF treatment, among these were CCL3, CCL4, CXCL10, CXCL13, IL-6 and PD-L1 (all adjusted p<0.05). All targets correlated with baseline CRP, and except for PD-L1, also with ASDAS, BASDAI and BASMI (all rho >0.4). Baseline CXCL13, IL-6 and PD-L1 also correlated to baseline spinal MRI inflammation (rho>0.4). Furthermore, baseline CXCL13 and IL-6 were associated with spinal MRI inflammation after one year of treatment (rho>0.4). CXCL13 was also increased in synovial fluid from lsSpA patients. CXCL13 was not increased in eSpA compared to HCs, but the receptor for CXCL13, CXCR5 was increased on CD4+ PBMCs from eSpA patients compared to HCs (17.3% vs 12.3%, p<0.01). eSpA CD4+ PBMCs did not differ from HC CD4+ PBMCs when investigating general activity markers, including CD69, CD25 and PD-1. Evaluating the central site of pathology, CXCL13 was highly expressed in the inflamed facet joints (Figure 1). Conclusion The multiomics analysis revealed multiple cytokines to be activated in eSpA patients. The early disease is characterized by T cell activity in combination with macrophage and monocyte attractive chemokines. CXCL13 stands out as a chemokine of particular interest, being increased both in eSpA, at the central- and peripheral site of pathology, and associated with structural changes in time. The CXCR5-CXCL13 axis could be an important new axis in understanding SpA disease pathology, serving both as a biomarker for disease severity and progression, but also lead to new targets of treatment. Figure 1. Image/graph: REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared. Keywords: Spondyloarthritis, Biomarkers DOI: 10.1136/annrheumdis-2023-eular.4272Citation: , volume 82, supplement 1, year 2023, page 228Session: Disease mechanisms in spondylarthritis (Poster Tours)