Work

Immune cells from people with axial spondyloarthritis have increased metabolic activity when compared to controls 3368

Year: 2025

Type: article

Abstract: Description Axial Spondyloarthritis (AS) is an autoinflammatory disease with increased inflammation isolated to the sacroiliac joints and spine. As current treatments are not curative and globally suppress the immune system, research that determines mechanism of disease can improve patient quality of life by leading to therapies that avoid mass immunosuppression. It is well known that activation of immune cells causes a metabolic switch towards glycolysis, leading us to ask if immune cells are more glycolytic in people with AS and if this metabolic circuit is responsible for the enhanced inflammatory function. We found that bulk PBMCs from people with AS have significantly increased glycolytic flux. As glycolysis can feed the ETC, we also examined mitochondrial flux and found that AS PBMCs have increased mitochondrial flux as well. This increase yields enhanced superoxide (SO) within the mitochondria across CD14+ monocytes, CD19+ B cells, CD16+ cells, and CD4+and CD8+ T cells. Ultimately, this heightened metabolic flux yields increased abundance of ATP for energy utilization. These data illustrate the presence of a hyper metabolic state in people with AS. Our SO data suggest this phenotype penetrates multiple cell populations. Identifying the metabolic flux of individual populations will show if this metabolic dysregulation is cell specific or system wide. Determining the origin of this programming is the next step to understanding disease pathogenesis and potential therapeutic targets. Funding Sources This work is supported by the Shear Family Foundation, the University of Colorado Division of Rheumatology T32, and the Cleo Meador and George R. Scott Endowed Chair in Hematology Research. Topic Categories Immune Mechanisms of Human Disease (HUM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1179