Background Subclinical gut inflammation has been demonstrated in patients with psoriatic arthritis (PsA) suggesting a role for the gut in the pathogenesis of inflammation in these patients. A key role for the IL-23, IL-17, IL-22 and IL-9 in the pathogenesis of psoriasis and psoriatic arthritis has been suggested, the immunologic abnormalities underlying subclinical gut inflammation in PsA are still undefined however.
Objectives This study was undertaken to investigate the expression and tissue distribution of IL-23 and of Th17,Th22 and Th9 related molecules in the subclinical gut inflammation of patients with PsA.
Methods Gut inflammation was assessed accordingly to De Vos et al (1). Quantitative gene expression analysis of Th1, IL-23/Th17, Th22 and Th9 responses was performed in intestinal biopsy samples obtained from 22 patients with PsA (12 with non-radiographic psoriatic axial SpA, 5 of them displaying HLA-27 positivity), 10 patients with HLA-27 positive-ankylosing spondylitis (AS), 10 patients with Crohn's disease (CD) and 20 healthy controls. IL-23, IL-17, IL-22 and IL-9 tissue distribution was also evaluated by immunohistochemistry.
Results Chronic ileal inflammation was observed in 15 PsA patients with no difference regarding axial or peripheral disease. The terminal ileum of PsA patients was characterized by a complex immunological signature. IL-23p19 m-RNA was not significantly over-expressed compared to controls but a clear Th17 and Th22 polarized immune response was demonstrable, at levels comparable to those observed in CD. Differently from CD and similarly to AS, Th1 cytokines were not significantly over-expressed in PsA. Conversely, a strong IL-23p19 and IL-22 expression in the absence of Th17 polarization was confirmed in AS gut. Unlike AS and CD, a strong and significant up-regulation of IL-9 immunologically characterized the gut of PsA patients. In particular, IL-9 immune-reactivity was observed among infiltrating mononuclear cells, high endothelial venules and Paneth cells. IL-9 mononuclear cells were demonstrated to be in large part Th9 cells. IL-9 over-expression was accompanied by significant Paneth cells hyperplasia.
Conclusions The strong IL-9/Th9 polarization seems to be the predominant immunological signature of subclinical gut inflammation in PsA. Our findings indicate however a complex immune-regulation occurring in the gut of PsA patients where Th17 and Th22 polarization seems also to occur.
De Vos M, Cuvelier C, Mielants H et al. Ileocolonscopy in seronegative SPondiloarthropathy. Gastroenterology 1989
Disclosure of Interest None declared