ArticleEBioMedicine2022
Comprehensive genetic and functional analyses of Fc gamma receptors influence on response to rituximab therapy for autoimmunity.
Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- The 2026 British Society for Rheumatology guideline for the management of children, young people and adults with systemic lupus erythematosus.Rheumatology (Oxford, England) · 2026Guideline
- The Association between Genetics and Response to Treatment with Biologics in Patients with Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, and Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Clinical presentations, treatments, and outcomes of pediatric lupus nephritis: a prospective cohort study from the Pediatric Nephrology Research Consortium.Pediatric nephrology (Berlin, Germany) · 2026Article
- Single-Cell Level Characterization of B Cell Depletion and Repopulation Following Rituximab in Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Toward Precision Oral Medicine in Pemphigus Vulgaris: A Conceptual AI Framework for Rituximab Response Prediction.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- B Cell Differentiation Model for Identifying Predictors of Responses to Rituximab-Mediated B Cell Depletion in Rheumatic Diseases.CPT: pharmacometrics & systems pharmacology · 2026Article
- A new, glycoengineered form of anti-CD20 monoclonal antibody, in treatment of multiple sclerosis.Therapeutic advances in neurological disorders · 2026Review
- Pharmacodynamics and Pharmacokinetics of Ublituximab Compared with Other Anti-CD20 Monoclonal Antibodies for Multiple Sclerosis Treatment.Current neuropharmacology · 2026Review
- Fcγ receptor expression on monocytes and association with etanercept efficacy in rheumatoid arthritis: a prospective cohort study.Frontiers in pharmacology · 2026Article
- Genetic variation of low-to-medium-affinity Fc-gamma receptors in Guillain-Barré syndrome.Journal of neurology · 2025Article
- The Evolution of Anti-CD20 Treatment for Multiple Sclerosis: Optimization of Antibody Characteristics and Function.CNS drugs · 2025Review
- B-Cell Depletion in Glomerular and Autoimmune Diseases: Too Much of a Good Thing?Kidney international reports · 2025Article
- Fc gamma receptor polymorphisms in antibody therapy: implications for bioassay development to enhance product quality.Antibody therapeutics · 2025Review
- Article
- Opportunities and limitations of B cell depletion approaches in SLE.Nature reviews. Rheumatology · 2025Review
- Comparison of the efficacy of thalidomide combined with low-dose rituximab and low-dose rituximab alone in the treatment of steroid-resistant/refractory adult patients with primary immune thrombocytopenia: an open-label trial.Frontiers in medicine · 2025Article
- Successful sequential therapy with rituximab and telitacicept in refractory Anti-NMDA receptor encephalitis and MOG-associated demyelination: a case report and literature review.Frontiers in immunology · 2025Review
- A rationally designed CD19 monoclonal antibody-triptolide conjugate for the treatment of systemic lupus erythematosus.Acta pharmaceutica Sinica. B · 2024Article
- Frequency of pharmacogenomic variants affecting safety and efficacy of immunomodulators and biologics in a South Asian population from Sri Lanka.Human genomics · 2024Article
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundRituximab is widely used to treat autoimmunity but clinical response varies. Efficacy is determined by the efficiency of B-cell depletion, which may depend on various Fc gamma receptor (FcγR)-dependent mechanisms. Study of FcγR is challenging due to the complexity of the FCGR genetic locus. We sought to assess the effect of FCGR variants on clinical response, B-cell depletion and NK-cell-mediated killing in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
methodsA longitudinal cohort study was conducted in 835 patients [RA = 573; SLE = 262]. Clinical outcome measures were two-component disease activity score in 28-joints (2C-DAS28CRP) for RA and British Isles Lupus Assessment Group (BILAG)-2004 major clinical response (MCR) for SLE at 6 months. B-cells were evaluated by highly-sensitive flow cytometry. Single nucleotide polymorphism and copy number variation for genes encoding five FcγRs were measured using multiplex ligation-dependent probe amplification. Ex vivo studies assessed NK-cell antibody-dependent cellular cytotoxicity (ADCC) and FcγR expression.
findingsIn RA, carriage of FCGR3A-158V and increased FCGR3A-158V copies were associated with greater 2C-DAS28CRP response (adjusted for baseline 2C-DAS28CRP). In SLE, MCR was associated with increased FCGR3A-158V, OR 1.64 (95% CI 1.12-2.41) and FCGR2C-ORF OR 1.93 (95% CI 1.09-3.40) copies. 236/413 (57%) patients with B-cell data achieved complete depletion. Homozygosity for FCGR3A-158V and increased FCGR3A-158V copies were associated with complete depletion in combined analyses. FCGR3A genotype was associated with rituximab-induced ADCC, and increased NK-cell FcγRIIIa expression was associated with improved clinical response and depletion in vivo. Furthermore, disease status and concomitant therapies impacted both NK-cell FcγRIIIa expression and ADCC.
interpretationFcγRIIIa is the major low affinity FcγR associated with rituximab response. Increased copies of the FCGR3A-158V allele (higher affinity for IgG1), influences clinical and biological responses to rituximab in autoimmunity. Enhancing FcγR-effector functions could improve the next generation of CD20-depleting therapies and genotyping may stratify patients for optimal treatment protocols.
fundingMedical Research Council, National Institute for Health and Care Research, Versus Arthritis.
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Registered trials
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