A recent study published in BMC Immunology reports that several key immune checkpoint molecules are significantly downregulated in the peripheral blood of patients with ankylosing spondylitis. The research, led by Kuang-Hui Yu and colleagues, examined the mRNA expression profiles of co-stimulatory and co-inhibitory signals in a cohort of 33 patients with ankylosing spondylitis and 28 healthy controls from the Taiwanese population. The findings suggest a coordinated reduction in both activating and inhibitory immune signals, a pattern that may reflect chronic immune exhaustion or the redistribution of activated immune cells to sites of inflammation within the body.
Ankylosing spondylitis is a chronic inflammatory autoimmune disease in which T-cell dysregulation plays a pivotal role in disease progression. A balance of co-stimulatory and co-inhibitory molecules governs the activation of T cells. To investigate how this balance is altered in ankylosing spondylitis, the researchers focused on the transcriptional levels of five specific co-stimulatory molecules: CD28, CD40, CD40L, OX40, and OX40L. They also included one co-inhibitory molecule, TIM-3, to assess the broader landscape of immune checkpoint signaling in these patients.
The study utilized quantitative reverse transcription polymerase chain reaction, or qRT-PCR, to quantify the mRNA expression levels of these molecules in blood samples. Relative expression was calculated via the 2−△△ct method, normalized to beta-actin.
The results revealed a significant downregulation of several immune checkpoint molecules in the ankylosing spondylitis patients compared to the healthy controls. Specifically, the patients exhibited a 2.67-fold reduction in CD28 expression, with a p-value of less than 0.0001, indicating a highly statistically significant difference. Similarly, CD40L showed a 2.37-fold reduction, also with a p-value of less than 0.0001.
In addition to the co-stimulatory molecules, the co-inhibitory molecule TIM-3 was also significantly downregulated, showing a 2.20-fold reduction with a p-value of less than 0.0001. CD40 expression was reduced by 1.47-fold, with a p-value of 0.006. However, the study did not find significant differences in the expression of OX40 and OX40L between the two groups.
The concurrent downregulation of both activating and inhibitory signals points toward a trend of coordinated downregulation within the immune checkpoint network. The authors propose that this phenomenon may represent chronic immune exhaustion. Alternatively, it could reflect the redistribution of activated immune cells to sites of inflammation.
The study identifies CD40L and TIM-3 as particularly interesting candidates for further investigation as potential biomarkers. The authors note that these molecules warrant further study in larger cohorts that are matched for age and sex to confirm the observed associations.
Subject of Research: Transcriptional analysis of co-stimulatory and co-inhibitory molecules in ankylosing spondylitis
Article Title: Transcriptional analysis of co-stimulatory molecules in ankylosing spondylitis
Article References: Yu, K.-H., Chao, C.-H., Wang, W.-T., & Chen, D.-P. (2026). Transcriptional analysis of co-stimulatory molecules in ankylosing spondylitis. BMC Immunology. https://doi.org/10.1186/s12865-026-00904-x
Image Credits: AI Generated
DOI: 10.1186/s12865-026-00904-x
Keywords: Ankylosing Spondylitis, Immune Checkpoints, T-cell Dysregulation, CD28, CD40L, TIM-3, qRT-PCR, Autoimmune Disease, Transcriptional Analysis, BMC Immunology, Transcriptional, analysis
News Source: Ophelia Keating. (November 7, 2026). Immune Checkpoint Molecules Downregulated in Ankylosing Spondylitis. Scienmag.
