Identification of pathogenic T cell clones in Enthesitis Related Arthritis
Project Period:
2025-2027
Grant Category:
Advancing Biosample Collection Grant
Disease Area:
Juvenile Idiopathic Arthritis (JIA), Juvenile Spondylarthritis (JSpA)
In adult spondyloarthritis (SpA), certain clonal T cells have been identified as associated with disease and able to recognize both bacterial and self-proteins when those proteins are presented to them by HLA-B27. One paper showed that depletion of just the clonal T cells, rather than all T cell, dramatically improved the symptoms and disease activity of one patient with HLA-B27+ Axial SpA (AxSpA). Despite these promising findings, such studies have not been attempted for children with Juvenile Axial Spondyloarthritis (JAxSpA). It is not known if children with JAxSpA harbor the same clonal T cells, and many are not HLA-B27+. The picture is further complicated by the fact that children with JAxSpA can have a different initial set of symptoms compared to adult onset Spondyloarthritis. Most children are initially diagnosed as Enthesitis Related Arthritis (ERA). 50% of children diagnosed with ERA go on to develop axial disease of the spine and sacroiliac joints within 5 years of diagnosis. Diagnosing axial disease requires magnetic resonance imaging (MRI), which in young children poses risks related to sedation. Using our internal NIAMS AxSpA biorepository and cohort, which is enriched for JAxSpA, we propose to look for clonal T cells reported from adult AxSpA in children. We will look for new and novel clonal T cells associated with HLA-B27+ AxSpA in children. In addition, we will look for new clonal T cell associations with SpA in patients who are not HLA-B27+. We will do all the above while this CARRA ABC award collection of 151 ERA samples is underway. Once the ABC award collection is complete, we propose to examine ERA samples for the clonal T cells we have identified in JAxSpA to see if clonal T cells can serve as a biomarker to differentiate which patient with ERA will develop JAxSpA and therefore who should have an MRI earlier rather than later. In this way clonal T cells may represent not only a biomarker of disease and but a test that can help triage timing and use of MRI. We also propose to evaluate the relationship between the frequency of peripheral blood clonal T cells and disease activity in both JAxSpA and in ERA that develops into JAxSpA. Such evidence that clonal T cells correspond to disease activity strengthens the argument that they would make an excellent therapeutic target.
Investigators

Sahar Lotfi-Emran, M.D., Ph.D.
National Institute of Arthritis, Musculoskeletal and Skin Diseases, NIH NIAMSRelated Awarded Grants
Disease Area:
Juvenile Idiopathic Arthritis (JIA)
Assessment of juvenile idiopathic arthritis outcomes and place of residence in Canada: identifying disparities in care
Disease Area:
Juvenile Idiopathic Arthritis (JIA)
Genetic Ancestry Powered studies (GAPs) in JIA
Disease Area:
Juvenile Idiopathic Arthritis (JIA)