ArticleArthritis research & therapy2013
A rheumatoid factor paradox: inhibition of rituximab effector function.
Article in Arthritis research & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Impact of rheumatoid factors on the function of therapeutic monoclonals specific for PD-1/PD-L1.Cancer immunology, immunotherapy : CII · 2025Article
- A phase 1 experimental medicine study of anti-CD3 monoclonal antibody in rheumatoid arthritis.Immunotherapy advances · 2025Article
- Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: the ANSWER cohort study.Rheumatology international · 2022Article
- Safety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis-associated Pulmonary Arterial Hypertension: A Multicenter, Double-Blind, Randomized, Placebo-controlled Trial.American journal of respiratory and critical care medicine · 2021Article
- Rheumatoid Factor: A Novel Determiner in Cancer History.Cancers · 2021Article
- Exploration and Evaluation of Therapeutic Efficacy of Drug-Free Macromolecular Therapeutics in Collagen-Induced Rheumatoid Arthritis Mouse Model.Macromolecular bioscience · 2020Article
- Usefulness of rheumatoid factor as an immunological and prognostic marker in PSS patients.Clinical rheumatology · 2019Article
- Structure-function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity.The Journal of biological chemistry · 2018Article
- Article
- Review
- Possible implication of Fc γ receptor-mediated trogocytosis in susceptibility to systemic autoimmune disease.Clinical & developmental immunology · 2013Review
- Rheumatoid factors: clinical applications.Disease markers · 2013Review
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionRituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC).
methodsWe developed an in vitro assay for RTX-CDC using patient sera and the Daudi human B cell line. Using propidium iodide uptake and flow cytometry, we compared RTX-CDC with rheumatoid factor (RF)+ sera relative to normal volunteer, non-RA and RF- sera. Additional studies examined mixing studies of RF+ and RF- sera, as well as the effect of monoclonal IgA or IgM RF. Finally, the effect of RF on RTX mediated trogocytosis of normal B cells was evaluated.
resultsUsing human sera, addition of RTX resulted in rapid and profound (>50%) Daudi cell death that was complement dependent. Surprisingly, RF+ patient sera exhibited reduced RTX-CDC relative to RF- sera, with an inverse relationship of RTX-CDC and RF titer. Mixing studies indicated the presence of an inhibitor of RTX-CDC in RF+ sera. The addition of monoclonal IgM or IgA RF to RF- sera markedly inhibited RTX-CDC. This effect was specific for RF binding to the Fc portion of RTX as it was not apparent with the F(ab)' domains of RTX engineered onto IgG3 heavy chain. RF also modestly inhibited RTX mediated trogocytosis.
conclusionsContrary to expectations, RF+ sera exhibits reduced RTX-CDC due to the presence of RF. The enhanced efficacy of RTX in seropositive RA patients cannot be attributed to improved B cell depletion through CDC. This result indicates that high RF levels may potentially modulate the efficacy of any therapeutic monoclonal antibody dependent on Fc effector function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.