Telomere protection biomarker for nutritional intervention in Spondyloarthritis

Overview

This research initiative addresses Spondyloarthritis (SpA), a group of related but phenotypically distinct chronic inflammatory diseases of unknown origin that include Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Reactive Arthritis, and arthritis associated with Inflammatory Bowel Disease. The project proposes to evaluate the telomere protection status of T-cells as a biomarker for the effect of nutrition in SpA patients. By linking T-cell immunosenescence, telomere shortening, and oxidative stress, the research aims to establish a measurable indicator of disease progression and treatment response. The work targets a critical unmet need: the lack of reliable biomarkers to unambiguously interpret how nutritional factors influence inflammation and oxidation in SpA.

Technical specifications

The research focuses on peripheral CD8+ T cells from SpA patients, which have been shown to exhibit spontaneous hypermotility correlating with a senescent, antigen-experienced, terminally differentiated immune phenotype and with telomere shortening and dysfunction. Key analytical approaches include:

• Transwell migration assays to isolate hypermigratory CD8+ T cells from patient peripheral blood mononuclear cells (PBMCs)
• RT-qPCR analysis to measure telomere length
• Immunofluorescence combined with telomeric FISH probes to detect telomeric DNA damage response markers, identifying telomere dysfunction
• Cytolytic enzyme and inflammatory cytokine profiling to characterize the "inflammascent" phenotype
• Clinical correlation with inflammatory markers (VES, PCR) and joint symptoms (pain and swelling)

Telomeres are oxidation-sensitive sites due to their abundance of guanines, which convert to 8-oxoguanines under oxidative stress, causing DNA breakage. The project hypothesizes that telomere attrition in T-cells results from unbalanced oxidation in the CD8+ subset exhibiting the inflammascent phenotype. Future validation will involve administering a low-energy diet supplemented with antioxidants (folic acid and vitamin D) versus a westernized Mediterranean diet over 8 months, with T-cell analysis at baseline, 4 months, 8 months, and 6 months post-diet.

Technology readiness level

The research has completed initial validation using 12 individuals per cohort (AS, PsA, Rheumatoid Arthritis, and healthy donors). Results confirmed that migrated CD8+ cells display an inflammascent phenotype with telomere shortening and dysfunction, with PsA and AS patients showing the most hypermigratory phenotype, highest cytolytic enzyme expression, and highest frequency of telomeric dysfunction. The project is now seeking partners interested in testing specific nutrients or antioxidants in this model system. Support is needed for research costs including reagents for cell culture, cytometry, immunofluorescence analysis, cell imaging, and personnel costs for sample collection and analysis.