Background/Purpose:

Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) have clear differences in clinical, radiological and genetic features, suggesting that the immunopathology of the conditions may also differ. IL-17/Th17 cells are thought to contribute to inflammatory arthritis as well as psoriasis. Given the strong association between MHC class I and PsA, we hypothesized that IL-17+ CD8+ T cells are enriched in PsA and correlate with disease activity and synovitis.

Methods:

Mononuclear cells from synovial fluid (SF) and peripheral blood (PB) compartments from 21 patients with PsA, 14 patients with RA and 14 healthy controls (PB only) were isolated and stimulated for three hours in vitro with PMA and ionomycin in the presence of GolgiStop. CD3+ T cells were investigated for expression of IL-17A by flow cytometry. Clinical measures and Power Doppler Ultrasound (PDUS) of the affected joint were assessed at the time of joint aspiration. PsA subjects were assessed by a blinded observer for erosive changes in hand and feet radiographs.

Results:

Both patients with PsA and RA had a significant increase in IL-17+ CD4+ T cells in the synovial fluid compared to their peripheral blood.  Notably, we also found a significant increase in IL-17 expressing cells in the CD4- compartment in SF from patients with PsA (SF vs. PB, median (IQR)%, 1.10 (0.46-2.29) vs. 0.18 (0.09-0.32), p=0.0002)) whilst this population was virtually absent in SF from patients with RA (p=0.83). The IL-17+ CD4- cells consisted predominantly of CD8+ T cells. No significant differences were found between IL-17+ T cell frequencies from the blood in patients with PsA vs. HC. SF IL-17+ CD4-(CD8+) T cells correlated significantly (Spearman’s r) with CRP (r= 0.57, p=0.005), ESR (r=0.62, p=0.002) as well as PDUS score of the affected joint (n=16, r=0.49, p=0.05), whilst SF IL-17+ CD4+ T cell frequency correlated only with ESR (r=0.42, p=0.05). Interestingly, patients with erosive disease (n=13) had elevated levels of IL-17+ CD3+CD4-(CD8+) cell frequencies in SF vs. non erosive subjects (n=8) (1.91 (1.03-4.94) vs. 0.32 (0.11-1.12), p<0.05, One-way ANOVA, post test: Dunn’s).  IL-17+ CD8+ T cells expressed low levels of perforin, granzyme B and CD107a in PB and SF (n=3) when compared to IFNγ+ CD8+ T cells, indicating that these cells may have a different effector function than cytotoxic CD8+ T cells.

Conclusion:

This is the first report documenting elevated IL-17+ CD3+CD4-(CD8+) cell frequencies in the PsA SF compartment with strong correlates with clinical and imaging measures of disease activity. We propose that IL-17+ CD8+ T cells may be a hitherto unrecognised population in PsA that may contribute to the immunopathology of this disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-17-cd8-t-cells-are-enriched-in-the-joints-of-patients-with-psoriatic-arthritis-and-correlate-with-markers-of-disease-activity-and-joint-damage-progression/