Type 17 specific immune pathways are active in early spondyloarthritis

Abstract

Background Undifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or other seronegative non-SpA inflammatory arthritides. Little is known about immune pathways active in the early stages of SpA and undifferentiated seronegative arthritis, in contrast to detailed knowledge of seropositive RA. We previously showed that synovial fluid (SF) IL-17A + CD8 + T cells (Tc17 cells) are enriched in patients with established SpA, but not RA. The aim of this study was to examine if specific immune pathways were active in synovial CD4 + and CD8 + T cells of patients with EIA. Methods SF samples from 30 patients with EIA were analysed, with final clinical diagnoses made at least 12 months after sample collection, by two independent clinicians blind to the study data. SF mononuclear cells were stimulated for 3 hours with PMA/ionomycin in the presence of GolgiStop, followed by staining for IL-17A, interferon-g and TNFa in CD8 + or CD4 + T cells. Results Flow cytometry analysis of all EIA samples indicated considerable variation in synovial Tc17 cell frequencies between patients. The group with a final diagnosis of SpA (PsA or peripheral SpA, n = 14) showed a significant enrichment in the percentage of synovial Tc17 cells compared with the group diagnosed with non-SpA seronegative inflammatory arthritides (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, a significant elevation in the percentage of CD8 + IFNg + T cells was seen in RA compared with seronegative SpA or non-SpA. Conclusions These results suggest that adaptive T cell cytokine pathways differ not only between RA and SpA but also non-SpA seronegative IA early in the disease process, with a particular activation of type 17 pathways in early SpA.