Comparative transcriptomic meta-analysis reveals elevated TCL1A expression in human circulating immune cells across...

Chronic pain affects millions worldwide. Its management is complicated by diverse risk factors, symptom variability, and the lack of biomarkers. Research often explores pain through the lens of the human immune system, as immune dysregulation may contribute to pain. However, most studies analyse both sexes together despite known sex differences in immune responses, with women facing higher risks of autoimmunity and chronic pain. Pooling data and adjusting for sex could obscure sex-specific immune signatures linked to chronic pain, limiting our understanding of its origins.

Using transcriptomic meta-analysis, we reprocessed several bulk RNA-sequencing studies of human circulating immune cells across multiple chronic pain conditions to examine both common and previously overlooked sex-specific transcriptomic signatures.

Our meta-analysis included bulk RNA-sequencing data from circulating immune cells of 142 patients with chronic pain and 154 control subjects across six chronic pain conditions. Combined-sex analysis revealed differential expression of 19 genes in chronic pain. Stratification by sex identified 34 altered genes in women, including TCL1A, which is implicated in autoimmunity. Notably, TCL1A expression correlated with neuropathic symptom severity (P<0.05). Protein-level validation in an independent cohort confirmed these findings in women with neuropathic pain.

Through transcriptomic meta-analysis of open-access data, we identified genes conserved across pain conditions and uncovered sex-specific signatures, including increased expression of TCL1A as a potential biomarker for neuropathic pain in a subset of women.