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The characterisation and regulation of type 1 immune responses in psoriatic arthritis
Arthritis Research & Therapy volume 4, Article number: 97 (2002)
Psoriatic arthritis (PsA) is a disabling inflammatory disease, of as yet unknown aetiology. A pathogenic role for TNF-α is suggested by the beneficial effects of anti-TNF therapy. However, upstream events remain to be elucidated. We propose that elevated levels of IFN-γ expression in inflamed PsA tissues, reflects a 'type 1' immune response, of pathophysiological significance. This study sought to identify and phenotype spontaneous IFN-γ secreting cells within PsA inflammatory lesions. Furthermore, we have elucidated factors, including costimulatory molecules and innate cytokines that regulate IFN-γ expression.
Matched PsA and rheumatoid peripheral blood (PB) and synovial fluid (SF) mononuclear cells were isolated on density gradients. Spontaneous IFN-γ secreting cells were identified using a novel bi-specific antibody capture method. T cells were further phenotypically characterised by FACS analysis. Following in vitro stimulation with mitogen/cytokines mononuclear cells were analysed for cytokine production by ELISA. Immunohistology on both skin and synovial membrane samples was performed using standard methods.
We have identified an increase in the percentage of spontaneous IFN-γ secreting cells in PsA synovial fluid when compared to rheumatoids. FACS analysis of PsA SF further identified cells expressing both CCR5 and IL-18R, characteristic of a Th1 phenotype. The presence of IL-12 and IL-18, potential inflammatory mediators, was confirmed in synovial membrane samples by immunohistochemistry. Furthermore, in vitro cultures of matched PsA PB/SF cells showed enhanced IFN-γ production by SF cells following stimulation with recombinant IL-12/IL-15. A threefold increase of IFN-γ was detected in the presence of CD3/CD28/IL-12 in SF compared with PBMC and a twelvefold increase in the presence of CD3/CD28/IL-15.
We have detected the presence and defined functional significance for the candidate regulatory cytokines, IL-12, IL-15 and IL-18 in sustaining IFN-γ expression. These findings support the hypothesis that PsA pathogenesis is associated with a 'type 1' polarised immune reponse.
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Gracie, J., Wilson, H., Robertson, S. et al. The characterisation and regulation of type 1 immune responses in psoriatic arthritis. Arthritis Res Ther 4, 97 (2002). https://doi.org/10.1186/ar544
- Synovial Fluid
- Psoriatic Arthritis
- FACS Analysis
- Costimulatory Molecule
- Synovial Fluid Cell