CONVENTIONAL THERAPY FOR EARLY INFLAMMATORY ARTHRITIS DOES NOT MODIFY PERIPHERAL BLOOD CYTOKINE PROFILES
Nicola J Gullick, David M Jayaraj, Hanan S Abozaid, Hayley G Evans, David L Scott, Ernest Choy, Leonie S Taams
Background: Many patients with early inflammatory arthritis (EIA) have inadequate responses to initial therapy, even if combination DMARDs and steroids are used at an early stage. We compared levels of cytokine expressing cells in EIA, established rheumatoid arthritis (RA) and healthy controls (HC), and followed EIA patients over 1 year to observe changes in disease activity and peripheral blood cytokines.
Peripheral blood mononuclear cells from HC (n=30), patients with EIA (n=20) or RA (n=38) were stimulated with PMA/Ionomycin for 3 hours then stained for cell markers and cytokines. Serum cytokines and chemokines were measured by luminex. Patients with EIA were reassessed at 6 and 12 months.
The percentage of IL-17+ CD4+ T cells was significantly increased in RA (median 0.59; IQR 0.38, 1.55) and EIA (0.81; 0.15, 1.46) vs HC (0.40; 0.24, 0.65; p 0.0043 by ANOVA, <0.05 for RA and EIA vs HC by Dunn’s post test). There were no significant increases in %IFNγ+CD4+ T cells, or %TNFα+ monocytes in either RA or IA vs HC. Serum IL-17, IL-1β, MIP-1α, and IL-2 were increased in RA and EIA vs HC, and IL-15 and IL-8 were increased in EIA vs HC. IL-6 and TNFα were increased in RA.
In EIA, %IL-17+CD4+ T cells at baseline was positively correlated with RF titre (r 0.587, p 0.01) and HAQ (r 0.574, p 0.03) at 12 months, and %IFNγ+CD4+ T cells was negatively correlated with baseline patient global assessment (r -0.673, p 0.01) and CRP (r -0.573, p 0.01). Baseline % IL-6+ monocytes was correlated with CRP at 12 months (r 0.603, p 0.01), but %TNFα+ monocytes was negatively correlated with both ESR (r -0.66, p 0.01) and TJ (r -0.52, p 0.03) at 12 months.
Mean DAS at baseline was 5.3 vs 4.5 after 12 months despite use of DMARDs ± steroids, similar to data from the methotrexate monotherapy arm in a large clinical trial1. There were no significant changes in cytokine expressing CD4+T cells over time, although %IL-6+ monocytes increased.
Conclusions: DMARDs, with or without corticosteroids do not impact significantly on presence of inflammatory cytokine producing T cells and monocytes in peripheral blood from patients with early inflammatory arthritis. This was accompanied by incomplete clinical response, suggesting that more intensive therapy is required early in the disease process.
1Choy et al Ann Rheum Dis 2008