Autoimmune rheumatologic diseases
Background: Ankylosing spondylitis (AS) is an HLA-B27-associated, inflammatory arthritis of the axial skeleton. Gut inflammation is a common co-morbidity in AS; the majority of AS patients have subclinical gut inflammation, while some have clinical inflammatory bowel disease (IBD). We hypothesize that inter-tissue trafficking of immune cells through shared trafficking receptors mediates the gut-joint axis of inflammation in AS.
Methods: We have examined the expression of trafficking markers by mass cytometry (CyTOF). Blood mononuclear cells from 26 AS patients, 20 healthy controls (HCs) and 17 rheumatoid arthritis (RA) patients, were surface stained using a 36-marker antibody panel. Cells from 6 AS and 3 RA synovial fluid samples and 2 IBD gut samples were also examined. Data was acquired on the CyTOF2 and analyzed using viSNE and Citrus algorithms
Results: In the blood, T cells from AS patients had a significant downregulation of CXCR3 and upregulation of CXCR4 compared to HC. A distinct population of integrin manifesting CD8+CD45RO+ T cells was seen in AS synovial fluid. These cells were characterized as CD103(aE)+CD49a(a1)+CD29(b1)+CD18(b2)+b7+. A similar population was enriched in IBD gut tissue, but not RA synovial fluid. Current experiments are being undertaken in the SKG and IL-23 minicircle mouse models of AS to identify and further characterize the integrin manifesting CD8+ T cells. Ã‚Â Ã‚Â
Conclusions: Unbiased analyses using CyTOF revealed disease- and tissue-specific alterations in trafficking marker expression in AS patient T cells. This technology allows for the identification of novel therapeutic targets to interfere with recruitment of potentially pathogenic cell subsets in AS.
Krembil Discovery Tower, University Health Network