Th55 - Impaired T Cell Mitochondrial Function and Metabolic Shifts in Glycolysis Characterize Axial Spondylarthritis

CD4+ T cells have been implicated in the pathogenesis of axial spondyloarthritis (axSpA), and in rodent models are sufficient to drive disease. With the aim of discovering unique features within CD4+ T cells, we analyzed previously published single-cell RNA sequencing data of PBMCs from two individuals with axSpA and two controls. The two most impacted pathways in T cells were oxidative phosphorylation and mitochondrial dysfunction (P< 1e-10) driven by downregulation in axSpA of critical genes in complexes 1, 3, 4 and 5. To assess T cell mitochondrial function in axSpA, we measured mitochondrial reactive oxygen species (ROS) using the flow-based MitoSOX assay (N=15). T cells in axSpA had significantly increased MitoSOX staining compared to controls (P=.011) with CD3+CD4+ showing 2.8 fold (P=0.004) and CD3+CD8+ T cells a 2.0 fold (P=0.005) increased mitochondrial ROS production. Next, we sought to understand how changes in T cell mitochondrial function were reflective of the general metabolomic profile of axSpA. We screened metabolites in serum of 23 patients with axSpA and 24 controls. Oxalosuccinate of the TCA cycle was significantly increased in patients with axSpA (P=7.86e-9) and multiple omega-3 fatty acids (hexadecanoic acid, octadecanoic acid, and docosahexaenoic acid) were all decreased compared to controls (FDR corrected P< .05 across tested metabolites), suggesting an impaired switch from glycolysis to oxidative phosphorylation. Together our results suggest mitochondrial dysfunction in T cells as well as overall metabolic dysfunction in patients with axSpA, opening an avenue for further study into the pathophysiology of axSpA.