Type 17-specific immune pathways are active in early spondyloarthritis

Hughes, C.D.; Ryan, S.E.; Steel, K.J.A.; Beukel, M.D. van den; Trouw, L.A.; Schie, K.A.J. van; Toes, R.E.M.; Menon, B.; Kirkham, B.W.; Taams, L.S.

doi:doi:10.1136/rmdopen-2023-003328

ObjectiveUndifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or remain as seronegative undifferentiated inflammatory arthritis (UIA). Little is known about immune pathways active in the early stages of SpA and seronegative UIA, in contrast to detailed knowledge of seropositive RA. The aim of this study was to examine if specific immune pathways were active in synovial CD4+ and CD8+ T cells in EIA.MethodsSynovial fluid (SF) samples from 30 patients with EIA were analysed for expression of IL-17A, IFN gamma and TNF alpha in CD8+ or CD4+ T cells. Final clinical diagnoses were made at least 12 months after sample collection, by two independent clinicians blind to the study data.ResultsFlow cytometry analysis of all EIA samples indicated considerable variation in synovial IL-17A+CD8+ T cells (Tc17) cell frequencies between patients. The group with a final diagnosis of SpA ...Show moreObjectiveUndifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or remain as seronegative undifferentiated inflammatory arthritis (UIA). Little is known about immune pathways active in the early stages of SpA and seronegative UIA, in contrast to detailed knowledge of seropositive RA. The aim of this study was to examine if specific immune pathways were active in synovial CD4+ and CD8+ T cells in EIA.MethodsSynovial fluid (SF) samples from 30 patients with EIA were analysed for expression of IL-17A, IFN gamma and TNF alpha in CD8+ or CD4+ T cells. Final clinical diagnoses were made at least 12 months after sample collection, by two independent clinicians blind to the study data.ResultsFlow cytometry analysis of all EIA samples indicated considerable variation in synovial IL-17A+CD8+ T cells (Tc17) cell frequencies between patients. The group with a final diagnosis of SpA (psoriatic arthritis or peripheral SpA, n=14) showed a significant enrichment in the percentage of synovial Tc17 cells compared with the group later diagnosed with seronegative UIA (n=10). The small number of patients later diagnosed with seropositive RA (n=6) patients had few Tc17 cells, similar to our previous findings in established disease. In contrast, RA SF contained a significantly higher percentage of CD8+IFN gamma+ T cells compared with SpA or seronegative UIA.ConclusionThese results suggest that adaptive T cell cytokine pathways differ not only between RA and SpA but also seronegative UIA early in the disease process, with a particular activation of Tc17 pathways in early SpA.Show less

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Type 17-specific immune pathways are active in early spondyloarthritis