Abatacept Reduces Foxp3 Positive Regulatory T-Cells in Psoriatic Arthritis Synovial Tissue; A Single Centre, Placebo- Controlled, Crossover Study
A. Szentpetery1, J. McCormack2, L. Mellerick3, E. Heffernan4, A. Fabre3, O. FitzGerald1
1Rheumatology, St. Vincent’s University Hospital 2Digital Pathology Core Facility, University College Dublin, Conway Institute, 3Histopatholog, St. Vincent’s University Hospital, Dublin, Ireland 4Diagnostic Imaging, St. Vincent’s University Hospital, Dublin, Ireland
Abatacept selectively inhibits T-cell activation via CD80/CD86:CD28 co-stimulation pathway and decreases serum levels of inflammatory cytokines implicated in the pathogenesis of psoriatic arthritis (PsA). Abatacept 3mg/kg dose was associated with better skin response, whilst 10 mg/kg dose showed better ACR response in PsA . Data is limited on the immunopathological effect of abatacept in PsA synovium.
(1) to study the change in immunohistochemical markers of synovial inflammation from baseline to 6 months after introducing abatacept in patients with active PsA; (2) to evaluate the impact of a short period of abatacept 3 mg/kg treatment on both skin and joint-related clinical outcomes compared to placebo (PBO); (3) to investigate if cell markers of synovial inflammation correlate to disease activity and MRI scores.
Biological-naïve PsA patients with active disease for >3 months with synovitis of a knee were enrolled. Patients were randomised to receive abatacept 3mg/kg or PBO infusion on day 1, 15 and 29; thereafter abatacept 10mg/kg was administered every 28 days for 5 months.
MRI and synovial biopsy of the involved knee were obtained at 0, 2 and 6 months. Immunohistological staining for CD3, CD4, CD8, FoxP3 and CD31 was performed and expression was scored on a 5 point scale using a semi-quantitative method .
FoxP3 (%/300 cells) and CD31 expression (positive vessels/10 HPF) was evaluated. The PsAMRIS semi-quantitative method was used to score MRI scans .
15 patients (8 female/7 male) with mean age of 45 years were recruited. Four patients were on methotrexate. 73% and 90% of patients were EULAR responders at 2 and 6 months. Synovial FOXP3 expression showed significant reduction page 49 (p=0.027) and there was a marked reduction in CD4 expression (p=0.073) at 6 months. Disease activity measures and cell markers did not show a significant difference between the treatment and PBO groups, improvement in MRI score in the first 2 months was greater in the treatment group (p=0.02). CD3 correlated with both disease activity and MRI scores.
Abatacept reduced CD4 positive T-cell expression in the synovium. This is the first study showing significant reduction in synovial FOXP3+ Treg expression in PsA patients treated with abatacept.