Circulating Monocytes are Associated with Centralized Pain in Patients with Rheumatoid Arthritis 2253199

Abstract Introduction Over half of patients with RA report clinically meaningful pain, despite treatment with disease-modifying antirheumatic drugs (DMARDs). While joint inflammation is a known cause of pain in patients with rheumatic diseases, emerging data indicate that many patients also suffer from centralized or nociplastic pain. There is a critical unmet need to characterize the altered cellular state that distinguish patients with centralized pain. Methods In this study, we recruited RA patients with minimal joint inflammation but varying levels of pain. All patients consented under the IRB protocol underwent quantitative sensory testing (QST) to assess centralized pain and provided blood for immune profiling using state-of-the-art multi-parameter flow cytometry with a custom panel designed to identify key immune cell types and activation states. Samples from patients in the study with the highest and lowest levels of nociplastic pain were additionally used to generate single-cell RNA-sequencing (scRNA-seq) libraries. The resulting sequencing data was processed with cellranger pipeline and analyzed using the Seurat package in R. Results We were able to collect 44 usable samples from patients who successfully consented and completed all study requirements. Supervised and unsupervised analysis of the multi-parameter flow data demonstrated that the proportions of monocyte subpopulations were positively correlated with pain levels. Moreover, preliminary analyses of scRNA-seq from 6 patients confirmed that the ratio of monocytes to T cells was increased in the high pain compared to the low pain group. Conclusion Our preliminary results indicate that monocytes are associated with centralized/nociplastic pain in RA patients. With further analysis, we aim to validate these results in the larger dataset and determine whether there are robust transcriptional changes in specific cell types. These studies provide novel insights into the role of circulating immune cells in altered CNS pain regulation in RA patients. Funding Source RRF, NIH Topic Categories Translational and Interventional Immunology (TI)