Th221 - Peripheral Immunome Dysregulations Reflect Osteoarthritis (OA) Joint Disease Severity

Gladys Ang, PhD – Research Fellow, Translational Immunology Institute; Ahmad Lajam – Research Officer, Translational Immunology Institute; Martin Wasser, PhD – Senior Biostatistician, Translational Immunology Institute; Pavanish Kumar – Biostatistician / Research Fellow, Translational Immunology Institute; Katy Leung – Associate Professor, Rheumatology and Immunology, Singapore General Hospital; Salvatore Albani – Professor, Translational Immunology Institute

Abstract Text: Osteoarthritis (OA) is a prevalent joint inflammatory condition that is especially common among older people. It is recognized that OA pathogenesis involves a complex interplay of joint damage, poor cartilage regeneration, and inflammation. However, how the peripheral immunome is perturbed by the local joint inflammation is not well understood. To investigate the peripheral immunome dysregulation in OA, we employed mass cytometry time-of-flight (CyTOF) to investigate peripheral blood mononuclear cells (PBMCs) obtained from patients with OA of varying severity (n = 64) and age, sex, and race-matched healthy controls (HCs) (n = 37). We observed peripheral immunome dysregulation that evolves with the disease severity of the OA joint. In early OA, inflammatory immune subsets such as natural killer (NK) and gamma-delta T cells were identified to be dysregulated suggesting the possibility of these subsets infiltrating the joint to initiate and perpetuate inflammation. As the disease progresses to late OA, we discovered further involvement of CD45RO+ and CTLA-4+/PD-1+ T cell subsets suggesting memory formation and immune exhaustion. Furthermore, we also observed an involvement of regulatory subsets in late OA suggesting the homeostatic attempts to temper the chronic inflammation. In silico deconvolution of RNA-sequencing data obtained from synovial samples revealed joint level immune dysregulations that mirror our peripheral immunome findings. Our study has revealed profound peripheral immunome changes that provide insights to the immunopathogenesis of OA. By uncovering the underlying peripheral immunome changes in OA, we provide further evidence that there is a significant immune component in the disease process of OA.