Abstract
Objectives
To investigate the association between the functional Fc gamma receptor 3 A (FCGR3A) V158F and FCGR2A R131H polymorphisms and rituximab therapy in patients with autoimmune diseases.
Methods
We searched the Medline, Embase, and Cochrane databases for relevant articles. We conducted a meta-analysis of the association between FCGR3A V158F and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases.
Results
Eleven studies, consisting of 661 responders and 267 non-responders for FCGR3A V158F polymorphism and 156 responders and 89 non-responders for FCGR2A R131H polymorphism, were included. The meta-analysis revealed a significant association between the FCGR3A V allele and responsiveness to rituximab (odds ratio [OR] = 1.600, 95% confidence interval [CI] = 1.268–2.018, P < 0.001). Furthermore, associations were found using the dominant and homozygous contrast models. Subgroup analysis showed an association between the FCGR3A V allele and responsiveness to rituximab in European, RA, ITP, small (<50) and large (≥50) groups, and short- (≤6 months) and long-term follow-up periods (≥6 months). These associations were also found in recessive, dominant or homozygous contrast models. Meta-analysis revealed no association between the FCGR2A R allele and responsiveness to rituximab (OR = 1.243, 95% CI = 0.825–1.873, P = 0.229).
Conclusions
We demonstrated that the FCGR3A F158V polymorphism is associated with better responsiveness to rituximab therapy in patients with autoimmune diseases, indicating that individuals carrying the FCGR3A V allele will likely respond better to rituximab. However, FCGR2A R131H polymorphism was not associated with better response to rituximab.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 print issues and online access
$259.00 per year
only $43.17 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Marrack P, Kappler J, Kotzin BL. Autoimmune disease: why and where it occurs. Nat Med. 2001;7:899–905.
Bruhns P. Properties of mouse and human IgG receptors and their contribution to disease models. Blood J Am Soc Hematol. 2012;119:5640–9.
Lee YH, Bae S-C, Song GG. The efficacy and safety of rituximab for the treatment of active rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials. Rheumatol Int. 2011;31:1493–9.
Choi SJ, Ahn SM, Oh JS, Hong S, Lee C-K, Yoo B, et al. Initial preserved renal function as a predictor of favorable renal response to rituximab in refractory or relapsing lupus nephritis: a single-center cohort study in Korea. J Rheum Dis. 2022;29:22–32.
Do H, Pyo JY, Song JJ, Park Y-B, Lee S-W. Implication of serious infections in patients with antineutrophil cytoplasmic antibody-associated vasculitis for the first cycle of rituximab: a pilot study in a single Korean center. J Rheum Dis. 2023;30:45–52.
Ravetch JV, Bolland S. IgG Fc receptors. Annu Rev Immunol. 2001;19:275–90.
Koene HR, Kleijer M, Algra J, Roos D, von dem Borne AE, de Haas, et al. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood. 1997;90:1109–14.
Sanders LA, Feldman RG, Voorhorst-Ogink MM, de Haas M, Rijkers GT, Capel PJ, et al. Human immunoglobulin G (IgG) Fc receptor IIA (CD32) polymorphism and IgG2-mediated bacterial phagocytosis by neutrophils. Infect Immun. 1995;63:73–81.
Jiménez Morales A, Maldonado‐Montoro M, Martinez de la Plata JE, Pérez Ramírez C, Daddaoua A, Alarcón Payer C, et al. FCGR2A/FCGR3A gene polymorphisms and clinical variables as predictors of response to tocilizumab and rituximab in patients with rheumatoid arthritis. J Clin Pharmacol. 2019;59:517–31.
Ellithy HN, Ahmed SH, Shahin GH, Matter MM, Talatt M. The impact of Fc gamma receptor IIa and IIIa gene polymorphisms on the therapeutic response of rituximab in Egyptian adult immune thrombocytopenic purpura. Hematology. 2018;23:169–74.
Pál I, Szamosi S, Hodosi K, Szekanecz Z, Váróczy L. Effect of Fcγ-receptor 3a (FCGR3A) gene polymorphisms on rituximab therapy in Hungarian patients with rheumatoid arthritis. RMD Open. 2017;3:e000485.
Cartin‐Ceba R, Indrakanti D, Specks U, Stone JH, Hoffman GS, Kallenberg CG, et al. The pharmacogenomic association of Fcγ receptors and cytochrome P450 enzymes with response to rituximab or cyclophosphamide treatment in antineutrophil cytoplasmic antibody–associated vasculitis. Arthritis Rheumatol. 2017;69:169–75.
Stork AC, Notermans NC, van den Berg LH, Schellevis RD, Niermeijer J-MF, Nederend M, et al. Fcγ receptor IIIA genotype is associated with rituximab response in antimyelin-associated glycoprotein neuropathy. J Neurol Neurosurg Psychiatry. 2014;85:918–20.
Quartuccio L, Fabris M, Pontarini E, Salvin S, Zabotti A, Benucci M, et al. The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumatoid arthritis: results of an Italian multicentre study. Ann Rheum Dis. 2014;73:716–21.
Zhu Y, Zhuang Y, Yang G-H, Qiang X-F, Yang L, Shen Y-F. Polymorphisms of FcγRIIA, FcγRIIIA and FcγRIIB in patients with immune thrombocytopenia and their clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013;21:135–9.
Kastbom A, Cöster L, Ärlestig L, Chatzidionysiou A, van Vollenhoven RF, Padyukov L, et al. Influence of FCGR3A genotype on the therapeutic response to rituximab in rheumatoid arthritis: an observational cohort study. BMJ Open. 2012;2;e001524.
Ruyssen-Witrand A, Rouanet S, Combe B, Dougados M, Le Loët X, Sibilia J, et al. Fcγ receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2012;71:875–7.
Robledo G, Márquez A, Dávila-Fajardo CL, Ortego-Centeno N, Rubio JLC, Garrido EDR, et al. Association of the FCGR3A-158F/V gene polymorphism with the response to rituximab treatment in Spanish systemic autoimmune disease patients. DNA Cell Biol. 2012;31:1671–7.
Cooper N, Stasi R, Cunningham‐Rundles S, Cesarman E, McFarland JG, Bussel JB. Platelet‐associated antibodies, cellular immunity and FCGR3a genotype influence the response to rituximab in immune thrombocytopenia. Br J Haematol. 2012;158:539–47.
Lee YH, Song GG. The gut microbiome and osteoarthritis: a two-sample mendelian randomization study. J Rheum Dis. 2021;28:94–100.
Lee YH. An overview of meta-analysis for clinicians. Korean J Intern Med. 2018;33:277.
Lee Y-H, Bae S-C, Song G-G. Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-analysis. Arch Med Res. 2012;43:356–62.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.
Egger M, Smith GD, Phillips AN. Meta-analysis: principles and procedures. BMJ. 1997;315:1533–7.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
Wells G, Shea B, O’connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2013. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.
Louis E, El Ghoul Z, Vermeire S, Dall’Ozzo S, Rutgeerts P, Paintaud G, et al. Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn’s disease. Alimentary Pharmacol Ther. 2004;19:511–9.
Arend WP. The innate immune system in rheumatoid arthritis. Arthritis Rheum. 2001;44:2224–34.
Liu D, Tian Y, Sun D, Sun H, Jin Y, Dong M. The FCGR3A polymorphism predicts the response to rituximab-based therapy in patients with non-Hodgkin lymphoma: a meta-analysis. Ann Hematol. 2016;95:1483–90.
Lee YH, Ji JD, Song GG. Associations between FCGR3A polymorphisms and susceptibility to rheumatoid arthritis: a metaanalysis. J Rheumatol. 2008;35:2129–35.
Choi SJ, Rho YH, Ji JD, Song GG, Lee YH. Genome scan meta-analysis of rheumatoid arthritis. Rheumatology. 2006;45:166–70.
Raychaudhuri S, Thomson BP, Remmers EF, Eyre S, Hinks A, Guiducci C, et al. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet. 2009;41:1313–8.
Su K, Wu J, Edberg JC, McKenzie SE, Kimberly RP. Genomic organization of classical human low-affinity Fcgamma receptor genes. Genes Immun. 2002;3:S51–6.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Lee, Y.H., Song, G.G. Association between functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases: a meta-analysis. Pharmacogenomics J 23, 210–216 (2023). https://doi.org/10.1038/s41397-023-00308-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41397-023-00308-9