[en] AIM: To test the hypothesis of an association between polymorphism in FCGR3A (the gene coding for FcgammaRIIIa, which is expressed on macrophages and natural killer cells, is involved in antibody-dependent cell-mediated cytotoxicity and has recently been associated with a positive response to rituximab, a recombinant immunoglobulin G1 antibody used in non-Hodgkin's lymphomas) and response to infliximab in Crohn's disease. METHODS: FCGR3A-158 polymorphism was determined using an allele-specific polymerase chain reaction assay in 200 Crohn's disease patients who had received infliximab for either refractory luminal (n = 142) or fistulizing (n = 58) Crohn's disease. Clinical and biological responses (according to C-reactive protein levels) were assessed in 200 and 145 patients, respectively. RESULTS: There were 82.9% clinical responders in V/V patients vs. 72.7% in V/F and F/F patients (N.S.). Globally, the decrease in C-reactive protein was significantly higher in V/V patients than in F carriers (P = 0.0078). A biological response was observed in 100% of V/V patients, compared with 69.8% of F carriers (P = 0.0002; relative risk, 1.43; 95% confidence interval, 1.27-1.61). In the sub-group of patients with elevated C-reactive protein before treatment, the multivariate analysis selected the use of immunosuppressive drugs and FCGR3A genotype as independent factors influencing the clinical response to infliximab (P = 0.003). CONCLUSION: Crohn's disease patients with FCGR3A-158 V/V genotype have a better biological and, possibly, clinical response to infliximab.
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Bibliography
Knight DM, Trinh H, Le J, et al. Construction and initial characterization of a human-mouse chimeric antibody. Mol Immunol 1993; 30: 1443-53.
Targan S, Hanauer S, van Deventer SJH, et al. A short term study of chimeric antibody cA2 to tumor necrosis factor alpha for Crohn's disease. N Engl J Med 1997; 337: 1029-35.
Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999; 340: 1398-405.
Cohen RD, Tsang JF, Hanauer SB. Infliximab in Crohn's disease: first anniversary clinical experience. Am J Gastroenterol 2000; 95: 3469-77.
Farrell RJ, Shah SA, Lodhavia PJ, et al. Clinical experience with infliximab therapy in 100 patients with Crohn's disease. Am J Gastroenterol 2000; 95: 3490-7.
Vermeire S, Louis E, Carbonez A, et al. Demographic and clinical parameters influencing the short-term outcome of anti-tumor necrosis factor (infliximab) treatment in Crohn's disease. Am J Gastroenterol 2002; 97: 2357-63.
Parsi MA, Achkar JP, Richardson S, et al. Predictors of response to infliximab in patients with Crohn's disease. Gastroenterology 2002; 123: 707-13.
Taylor KD, Plevy SE, Yang H, et al. Anca pattern and LTA haplotype relationship to clinical responses to anti-TNF antibody treatment in Crohn's disease. Gastroenterology 2001; 120: 1347-55.
Louis E, Vermeire S, Rutgeerts P, et al. A positive response to infliximab in Crohn's disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism. Scand J Gastroenterol 2002; 37: 818-24.
Mascheretti S, Hampe J, Kuhbacher T, et al. Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with chronic active Crohn's disease treated with infliximab. Pharmacogenomics J 2002; 2: 127-36.
De Silva A, Vermeire S, Ahmad T, et al. Pharmacogenetics of infliximab in Crohn's disease: the 5q31/IBD5 risk haplotype predicts response. Gastroenterology 2002; 122: M1423.
Vermeire S, Louis E, Rutgeerts P, et al. NOD2/CARD15 does not influence response to infliximab in Crohn's disease. Gastroenterology 2002; 123: 106-11.
Mascheretti S, Hampe J, Croucher PJ, et al. Response to infliximab treatment in Crohn's disease is not associated with mutations in the CARD15 (NOD2) gene: an analysis in 534 patients from two multicenter, prospective GCP-level trials. Pharmacogenetics 2002; 12: 509-15.
Lorenz HM, Antoni C, Valerius T, et al. In vivo blockade of TNF-alpha by intravenous infusion of a chimeric monoclonal TNF-alpha antibody in patients with rheumatoid arthritis. Short-term cellular and molecular effects. J Immunol 1996; 156: 1646-53.
Geboes K, Dalle I, Baert F, D'Haens G, Cornillie F, Rutgeerts P. Mucosal distribution of infliximab in patients with Crohn's disease. Gastroenterology 2001; 120: A1664.
Baert FJ, D'Haens G, Peeters GR, et al. Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileo-colitis. Gastroenterology 1999; 116: 22-8.
Lügering A, Schmidt M, Lügering N, Pauels AG, Domschke W, Kucharzik T. Infliximab induces apoptosis in monocytes from patients with chronic active Crohn's disease by using a caspase-dependent pathway. Gastroenterology 2001; 121: 1145-57.
Scallon BJ, Moore MA, Trinh H, Knight DM, Ghrayeb J. Chimeric anti-TNF-alpha monoclonal antibody cA2 binds recombinant transmembrane TNF-alpha and activates immune effector functions. Cytokine 1995; 7: 251-9.
Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 1994; 83: 435-45.
Flieger D, Renoth S, Beier I, Sauerbruch T, Schmidt-Wolf I. Mechanism of cytotoxicity induced by chimeric mouse human monoclonal antibody IDEC-C2B8 in CD20-expressing lymphoma cell lines. Cell Immunol 2000; 204: 55-63.
Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 2000; 6: 443-6.
Koene HR, Kleijer M, Algra J, Roos D, von dem Borne AE, de Haas M. FcγRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell FcγRIIIa, independently of the FcγRIIIa-48L/R/H phenotype. Blood 1997; 90: 1109-14.
Wu J, Edberg JC, Redecha PB, et al. A novel polymorphism of FcγRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J Clin Invest 1997; 1000: 1059-70.
Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 2002; 99: 754-8.
Weng WK, Levy R. Two immunoglobulin G Fc receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol 2003; 21: 3940-7.
Su K, Wu J, Edberg JC, McKenzie SE, Kimberly RP. Genomic organization of classical human low-affinity Fcγ receptor genes. Genes Immunity 2002; 3(Suppl. 1): S51-6.
Leppers-van de Straat FG, van der Pol WL, Jansen MD, et al. A novel PCR-based method for direct Fc gamma receptor IIIa (CD16) allotyping. J Immunol Methods 2000; 242: 127-32.
Dall'Ozzo S, Andrès C, Bardos P, Watier H, Thibault G. Rapid single-step FCGR3A genotyping based on SYBR Green I fluorescence in real-time multiplex allele-specific PCR. J Immunol Methods 2003; 277: 185-92.
Solberg HE. Approved recommendation on the theory of reference values. Part 5. Statistical treatment of collected reference values. Determination of reference limits. J Clin Chem Clin Biochem 1987; 25: 645-56.
Cellier C, Sahmoud T, Froguel E, et al. Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. Gut 1994; 35: 231-5.
D'Haens G, Van Deventer S, Van Hogezand R, et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European multicenter trial. Gastroenterology 1999; 116: 1029-34.
Siegel SA, Sheay DJ, Nakada MT, et al. The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. Cytokine 1995; 7: 15-25.
Sandborn WJ, Hanauer SB, Katz S, et al. Etanercept for active Crohn's disease: a randomised, double-blind, placebo-controlled trial. Gastroenterology 2001; 121: 1088-94.
Van den Brande J, Braat H, van den Brink G, et al. Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease. Gastroenterology 2003; 124: 1774-85.
Barone D, Krantz D, Maiori K, Moler K. Comparative analysis of the ability of etanercept and infliximab to lyse TNF-expressing cells in a complement-dependent fashion. Arthritis Rheum 1999; 42(Suppl.): S90.
Shen C, Colpaert S, Maerten P, et al. Infliximab induces death of human monocytes in vitro and in the THP-1-SCID-mouse model. Clin Immunol Suppl 2003; 1: S142.
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