Justyna Chwiecko

Soluble adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and vascular endothelial growth factor (VEGF) in patients with distinct variants of rheumatoid synovitis

Background: Cell adhesion molecules and endothelial growth factors have an important role in the infiltrating of rheumatoid synovium with mononuclear cells, leading to the initiation and progression of the disease. Objective: To investigate whether the serum profile of soluble adhesion molecules and of vascular endothelial growth factor (VEGF) is associated with the histological appearance of rheumatoid arthritis (RA). Methods: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were assessed by enzyme linked immunosorbent assay (ELISA) in 40 patients with RA and 32 patients with osteoarthritis (OA). Results: Histological analysis of synovium specimens distinguished two types of rheumatoid synovitis. Twenty four RA samples presented diffuse infiltrates of mononuclear cells without any further microanatomical organisation, whereas in the remaining 16 samples lymphocytic follicles with germinal centre-like structures were identified. In comparison with patients with OA, constituting a control group, higher serum concentrations of sICAM-1 (p<0.001), sVCAM-1 (p<0.001), sE-selectin (p<0.01), and VEGF (p<0.001) were detected in patients with RA. Raised concentrations of sICAM-1, sVCAM-1, and VEGF dominated in the serum of patients with RA with follicular synovitis compared with those with diffuse synovitis (p<0.01 for all comparisons). The serum concentrations of sICAM-1, sVCAM-1, and VEGF correlated with markers of disease activity such as the erythrocyte sedimentation rate and C reactive protein levels. Furthermore, the clinical data analysed in our study indicated that patients with RA with follicular synovitis tend to have more severe disease. Conclusions: The distinct histological appearances of rheumatoid synovitis associated with different serum profiles of sICAM-1, sVCAM-1, and VEGF reflect varied clinical activity of the disease and confirm RA heterogeneity. Patients with different histological forms of synovitis may respond differently to the treatment regimens.

Circulating tumour necrosis factor α and soluble tumour necrosis factor receptors in patients with different patterns of rheumatoid synovitis

Objective: To examine the relation between the serum levels of tumour necrosis factor α (TNFα), soluble tumour necrosis factor receptors (sTNF-R), and the histological pattern of rheumatoid synovitis. Methods: An enzyme linked immunosorbent assay (ELISA) was used to measure TNFα, p55 sTNF-R, and p75 sTNF-R concentrations in the serum of 43 patients with rheumatoid arthritis (RA) and 34 patients with osteoarthritis (OA). Results: Upon histological analysis two variants of rheumatoid synovitis emerged. Twenty six RA specimens presented only diffuse infiltrates of mononuclear cells. In the remaining 17 samples the formation of lymphocytic follicles with germinal centre-like structures was found. Serum concentrations of TNFα, p55 and p75 sTNF-R were raised in patients with RA compared with the OA control group (p<0.001 for all comparisons). Levels of TNFα, p55 and p75 sTNF-R were higher in the serum of patients with RA with follicular synovitis than in patients with diffuse synovitis (p<0.001, p<0.01, and p<0.05, respectively). Serum concentrations of TNFα, p55 and p75 sTNF-R correlated with markers of disease activity. Conclusion: Different histological types of rheumatoid synovitis associated with distinct serum levels of TNFα and sTNF-R reflect varying clinical activity of the disease and support the concept of RA heterogeneity.

Soluble cell adhesion molecules (sICAM‐1, sVCAM‐1, and sE‐selectin) in patients with early rheumatoid arthritis

Objective: The aim of the study was to analyse serum concentrations of soluble cell adhesion molecules (CAMs) in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). Methods: We studied 32 RA patients, untreated with disease‐modifying anti‐rheumatic drugs (DMARDs) or corticosteroids, with disease duration less than 3 years. Twenty osteoarthritis (OA) patients constituted the control group. The analysis of serum levels of soluble intercellular adhesion molecule‐1 (sICAM‐1), vascular cell adhesion molecule‐1 (sVCAM‐1), and E‐selectin (sE‐selectin) was based on a quantitative sandwich enzyme‐linked immunosorbent assay (ELISA). Results: In comparison with OA patients, higher serum concentrations of sICAM‐1 (p<0.01), sVCAM‐1 (p<0.01), and sE‐selectin (p<0.05) were observed in untreated patients with early RA. Six months of treatment with MTX down‐regulated serum concentrations of sICAM‐1, sVCAM‐1, and sE‐selectin (in all cases p<0.001) in the RA patients studied. MTX treatment was also followed by a decrease in the clinical markers of RA activity, such as the number of painful and swollen joints, erythrocyte sedimentation rate (ESR), disease activity score (DAS), and C‐reactive protein (CRP) levels. Conclusions: Patients with early RA are characterized by high serum concentrations of sICAM‐1, sVCAM‐1, and sE‐selectin. Therapy with MTX resulted in clinical improvement and diminished serum levels of soluble CAMs in the RA patients studied, confirming the effectiveness of MTX in early stages of the disease.

Effect of etanercept on serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, and sE-selectin) and vascular endothelial growth factor in patients with rheumatoid arthritis.

Objective: Endothelium and adhesion molecules are engaged in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to analyse the effect of etanercept on the levels of soluble cell adhesion molecules (sCAMs) and vascular endothelial growth factor (VEGF) in patients with active RA. Methods: Patients were receiving 50 mg/week of subcutaneous etanercept and 10–25 mg/week of methotrexate (MTX). Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) in 18 RA patients (prior to injection) at 0, 3, 6, 9, and 12 months. Results: A decrease in serum levels of sICAM-1 (p<0.001), sVCAM-1 (p<0.01), sE-selectin (p<0.01), and VEGF (p<0.001) was observed in RA patients after 3 months of treatment with etanercept. Six months of therapy with etanercept prolonged the suppression of serum sICAM-1 (p<0.01) and even more remarkably diminished sVCAM-1, sE-selectin, and VEGF (in all cases p<0.001) concentrations as compared to baseline (month 0). Treatment also effectively diminished sICAM-1, sVCAM-1, and VEGF levels at months 9 and 12 (in all cases p<0.001), and less significantly sE-selectin (p<0.05 at month 9 and p<0.01 at month 12). The Disease Activity Score including a 28-joint count (DAS28) measured at 3, 6, 9, and 12 months decreased significantly compared to baseline (in all cases p<0.001). Conclusion: Our study shows that, besides a rapid suppression of disease activity, serum sCAM and VEGF concentrations are downregulated following anti-tumour necrosis factor alpha (TNFα) therapy combined with MTX. Prolonged treatment with etanercept sustained or even more remarkably diminished the sCAM and VEGF serum concentrations.

AB0447 Regulation of Serum Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases-1 following Rituximab Therapy in Patients with Rheumatoid Arthritis Refractory to Anti-Tumor Necrosis Factor Blockers

Background Serum matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important role in the pathogenesis of rheumatoid arthritis (RA). Objectives In our article we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20+ B cells, on the serum MMPs and TIMP-1 levels in patients with active RA not responding to anti-tumor necrosis factor (anti-TNF) therapy. Methods Twelve RA patients were planned to receive 4 infusions of 1000mg of rituximab at weeks 0, 2, 24, and 26. The therapy was combined with methotrexate (MTX) (20-30mg/week). Seven patients were refractory to previously received infliximab, and 5 to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Results Initial infusion of rituximab down-regulated serum MMP-1 (p<0.01), MMP-3 (p<0.001), MMP-9 (p<0.001) and TIMP-1 (p<0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p<0.001 in all cases) and TIMP-1 level (p<0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Conclusions Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1496