Session Title: T cell Biology in Rheumatoid Arthritis and Other Arthritis
Session Type: Abstract Submissions (ACR)
The pro-inflammatory Th17 associated cytokines IL-17A and IL-22 have been proposed as important mediators of the inflammation seen in spondyloarthritis (SpA) and inflammatory bowel disease (IBD). A strong link between the development of SpA and IBD has been established, with Th17 cells as presumed pivotal players in the co-development of these inflammatory diseases. The aim of this study was to investigate differences in Th17 expression between SpA patients with subclinical gut inflammation, and SpA patients without gut inflammation. Further, changes in Th17 levels with anti-TNFα-therapy was investigated.
Thirty SpA patients with high (>100 mg/kg, n=15) and with normal (<50 mg/kg, n=15) fCal, and 14 healthy controls (HC) were included in this study. Patients with known psoriasis or IBD at the time of enrollment were excluded. All patients were eligible for anti-TNFα treatment, which was initiated at the day of enrolment in the study continuing for 52 weeks. During treatment mean BASDAI changed from 60 + 66 at baseline to 15 + 21 at 52 weeks. At baseline patients were clinically examined and all had a capsular endoscopy done and fCal was measured. Peripheral blood mononuclear cells (PBMCs) were isolated at baseline and at week 12, 20 and 52. Multicolour flow cytometry was performed in order to evaluate percentage of IL-17A, IL-22 and IL-23R expressing CD45RO T cells. Further, PBMCs were analysed for the expression of the Th17 defining chemokine receptor 6 (CCR6) and the gut-homing integrin complex alfa4-beta7.
Similar percentages of IL-17A, IL-22 and CCR6 expressing CD45RO T cells between SpA patients with high or low faecal calprotectin were observed. No difference in the gut homing potential of the IL-17A and IL-22 expressing T cells in either of the SpA groups evaluated as CD3+CD4+CD45RO+ lymphocytes double positive for alfa4 and beta7, was observed.
Since no differences in the two groups were observed, they were merged and further evaluated as one. Percentages of IL-17A+ 2.0% (1.4% – 2.4%), IL-22+ 2.9% (2.0% – 4.2%) and CCR6+ 20% (14.4% – 24.3%) CD45RO T cells at baseline was elevated compared to HCs IL-17A 1.16% (0.8%- 1.5%), IL-22 1.7% (1.0% – 2.3%) CCR6 9.5% (7.7% – 15.7%), respectively.
Despite major clinical improvement in the treatment period, the percentage of IL-17A+ CD45RO T cells increased to 3.1% (2.0% – 4.8%), IL-22+ CD45RO T cells increased to 3.8% (2.5%- 5.3%) and CCR6+ CD45RO T cells increased to 24.1% (18.7% – 27.1%) after 52 weeks of anti-TNFα therapy. No change in the percentage of alfa4/beta7+ or IL-23R+ CD45RO T cells was observed at any time-point.
Anti-TNFα therapy improved clinical disease activity of the SpA patients substantially. Surprisingly, underlying inflammatory activity, in the form of Th17/22 cells persisted, even 1 year after initiation of anti-TNFα therapy. The persistently elevated levels of Th17 cells could be involved in the on-going disease progression seen in SpA patients even with clinically low, and well-controlled disease activity.
Janssen Pharmaceutica Product, L.P.,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-tnf%ce%b1-treatment-increases-il-17a-and-il-22-t-cells-in-spondyloarthritis-regardless-of-concomittant-gut-inflammation/