POS0286 PROTEOMIC INSIGHTS INTO RADIOGRAPHIC PROGRESSION IN AXIAL SPONDYLOARTHRITIS
Authors: N. Barbarroja, I. Arias-de la Rosa, L. Cuesta-López, M. L. Ladehesa-Pineda, M. Ruiz-Ponce, A. Barranco, M. Á. Puche-Larrubia, C. Perez-Sanchez, M. D. C. Abalos-Aguilera, D. Ruiz-Vilchez, P. Ortiz-Buitrago, C. Lopez-Pedrera, A. Escudero-Contreras, E. Collantes-Estevez, C. López-Medina
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Radiographic assessment plays a crucial role in diagnosing and monitoring axial Spondyloarthritis (axSpA). Structural changes, such as erosions, sclerosis, and syndesmophytes, provide insights into the severity and impact of the disease on the axial skeleton. Understanding the molecular mechanisms driving radiographic progression is essential for developing targeted therapies and improving patient outcomes. Identifying biomarkers associated with radiographic progression can aid in early detection, risk stratification, and the development of personalized treatment strategies for patients with axSpA. <h3>Objectives:</h3> <b>1</b>) to assess the radiographic progression of axSpA over a span of five years and <b>2</b>) to examine the clinical and molecular aspects associated with radiographic progression in axSpA. <h3>Methods:</h3> a cohort of 70 axSpA patients was recruited at the Reina Sofia Hospital (Córdoba, Spain). Clinical and analytical variables were recorded. Blood extraction was carried out for the subsequent analysis of the serum levels of 184 proteins using Olink technology. The enriched biological functions of the identified altered proteins were assessed using the STRING platform. Structural damage, assessed using the "modified Stoke Ankylosing Spinal Score" (mSASSS), was examined at the time of the visit and in the preceding five years. Radiographic progression was quantified as Δ mSASSS (mSASSS at visit – mSASSS on the preceding 5 years). AxSpA progressors were determined using the following formula: Δ mSASSS/ years (with a cut-off value of &gt; 1 mSASSS). Statistically significant analyses were defined by a <i>p</i>-value &lt; 0.01. <h3>Results:</h3> out of 70 axSpA patients, 26 exhibited an annual increment of more than 1 point in mSASSS, categorizing them as progressors, while the remaining 44 were classified as non-progressors. There were no differences in age, sex, disease duration, disease activity, acute phase reactants, and HLA-B27 positivity among groups of progressors or non-progressors. However, levels of alkaline phosphatase (ALP) were significantly elevated in axSpA progressors compared to non-progressors. Remarkably, molecular analyses identified 12 proteins that were significantly differentially elevated in the progressor group compared to non-progressors (GRN, IL-2RA, KLK-6, IL-18BP, LTBR, IGFBP-7, TNFSF-13B, GDF-15, IL-10RA, IL-2, IL2Rβ, and IL-10). Furthermore, these proteins exhibited significant correlations with Δ mSASSS over the preceding 5 years. Additionally, levels of IL2RA, IL2Rβ, GDF-15, and IL-18BP significantly correlated with ALP. These findings may imply the potential engagement of these proteins in the development of structural damage and, consequently, radiographic progression in axSpA. The biological enrichment analysis of the altered proteins in progressors compared to non-progressors unveiled a significant protein-protein interaction enrichment (p-value=1.14e-09). Among the prominently enriched biological processes were the positive regulation of plasma cell differentiation, the regulation of T cell homeostatic proliferation, and the regulation of B cell apoptotic processes. These findings imply an exaggerated immune system, potentially linked to structural damage. Notably, IL-2 stood out significantly across all enrichment analyses, encompassing molecular functions, cellular components, KEGG pathways, and reactome pathways. <h3>Conclusion:</h3> <b>1</b>) The progression of structural damage in axSpA is intricately linked with the levels of ALP, a routine clinical follow-up variable; <b>2</b>) a distinctive molecular signature associated with radiographic progression has unveiled novel candidate biomarkers indicative of the evolving structural damage landscape in axSpA; <b>3</b>) the identified proteins exhibit enrichments in biological functions suggestive of a significant immune component potentially influencing structural damage. Notably, the IL-2 signalling pathways may play a pivotal role, underscoring their potential importance in the molecular mechanisms orchestrating radiographic progression in axSpA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Supported the "Instituto de Salud Carlos III" (PMP21/00119 and RICOR-RD21/0002/0033) co-financed by the European Union. <h3>Disclosure of Interests:</h3> <b>None declared.</b>