45 research outputs found
Prostaglandin E-2 Synthesizing Enzymes in Rheumatoid Arthritis B Cells and the Effects of B Cell Depleting Therapy on Enzyme Expression
Clinical response, pharmacokinetics, development of human anti-chimaeric antibodies, and synovial tissue response to rituximab treatment in patients with rheumatoid arthritis
Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity
Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity
Objectives Immunoglobulin (Ig) free light chains (FLCs) are short-lived B cell products that contribute to inflammation in several experimental disease models. In this study, FLC concentrations in inflamed joints of patients with rheumatoid arthritis (RA) as compared to patients with osteoarthritis were investigated. In addition, the relationship of FLCs and disease activity upon B cell depletion (rituximab) in patients with RA was studied. Methods Synovial fluid (SF) and tissue from patients with RA were analysed for local presence of FLCs using ELISA and immunohistochemistry. In addition, FLC concentrations were measured (at baseline, 3 and 6 months after treatment) in 50 patients with RA with active disease who were treated with rituximab. Changes in FLCs were correlated to changes in disease activity and compared to alterations in IgM, IgG, IgA, IgM-rheumatoid factor (RF) and IgG-anti-citrullinated protein antibody (ACPA) concentrations. Results FLCs were detected in synovial tissue from patients with RA, and high FLC concentrations were found in SF from inflamed joints, which positively correlate with serum FLC concentrations. Serum FLC concentrations significantly correlated with disease activity score using 28 joint counts, erythrocyte sedimentation rate (ESR) and C reactive protein, and changes in FLC correlated with clinical improvement after rituximab treatment. Moreover, effect of treatment on FLC concentrations discriminated clinical responders from non-responders, whereas IgM-RF and IgG-ACPA significantly decreased in both patient groups. Conclusions FLCs are abundantly present in inflamed joints and FLC levels correlate with disease activity. The correlation of FLC concentrations and disease activity indicates that FLCs may be relevant biomarkers for treatment response to rituximab in patients with RA and suggests that targeting FLC may be of importance in the therapy of R
A single course of rituximab does not abrogate anti-infliximab antibodies in patients with rheumatoid arthritis
Effect of rituximab treatment on T and B cell subsets in lymph node biopsies of patients with rheumatoid arthritis
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205472.pdf (publisher's version ) (Open Access)OBJECTIVES: The exact underlying mechanism of rituximab treatment in patients with RA is poorly defined and knowledge about the effect of B cell depletion on immune cells in secondary lymphoid organs is lacking. We analysed lymphoid tissue responses to rituximab in RA patients. METHODS: Fourteen RA patients received 2 x 1000 mg rituximab intravenously, and lymph node (LN) biopsies were obtained before and 4 weeks after the first infusion. Tissues were examined by flow cytometry, immunohistochemistry and quantitative PCR. LN biopsies from five healthy individuals (HC) served as controls. RESULTS: LN biopsies of RA patients showed increased frequencies of CD21+CD23+IgDhighIgMvariable follicular B cells and CD3+CD25+CD69+ early activated, tissue resident T cells when compared with HCs. After treatment, there was incomplete depletion of LN B cells. There was a significant decrease in CD27-IgD+ naive B cells, and CD27+IgD+ unswitched memory B cells including the CD27+IgD+IgM+ subset and follicular B cells. Strikingly, CD27+IgD- switched memory B cells persisted in LN biopsies after rituximab treatment. In the T cell compartment, a significant decrease was observed in the frequency of early activated, tissue resident T cells after rituximab treatment, but late activated T cells persisted. B cell proliferation inducing cytokine IL-21 was higher expressed in LN biopsies of RA patients compared with HC and expression was not affected by rituximab treatment. CONCLUSION: Rituximab does not cure RA, possibly due to persistence of switched memory B cells in lymphoid tissues suggesting that factors promoting B cell survival and differentiation need to be additionally targeted
Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab
B cells and B cell directed therapies in rheumatoid arthritis: towards personalized medicine
Rituximab is een monoklonaal antilichaam (een stof die gericht één type cel of eiwit kan uitschakelen) dat gebruikt wordt voor de behandeling van reumatoïde artritis (RA). Om onbekende redenen knappen echter niet álle RA-patiënten op van de biological. Rogier Thurlings onderzocht bij 40 patiënten het synovium (weefsel aan de binnenkant van het gewricht dat de gewrichtsvloeistof produceert) na een kuur met rituximab. Uit genetische analyses bleek dat B-cellen in het gewricht niet bij alle patiënten verdwenen. Met name het verdwijnen van plasmacellen (B-cellen in hun eindstadium, wanneer ze antistoffen maken) bleek te voorspellen of patiënten wel of niet reageren op de behandeling. Patiënten bij wie rituximab onvoldoende deed, hadden ook witte bloedcellen die sterk geactiveerd waren door ontstekingsfactor type I interferon, een stof die de overleving van B-cellen stimuleert