Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease.

• Abstract: 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.
• Authors: E Louis, Z El Ghoul, S Vermeire, S Dall'Ozzo, P Rutgeerts, G Paintaud, J Belaiche, M De Vos, A Van Gossum, J-F Colombel, H Watier (Affiliation: Department of Gastroenterology, CHU of Liège, Liège, Belgium.)
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 19 Issue 5 Pg. 511-9 (Mar 1 2004) ISSN: 0269-2813 [Print] England
• PMID: 14987319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Gastrointestinal Agents
• Receptors, IgG
• infliximab

Topics

• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• Crohn Disease (drug therapy, genetics)
• Female
• Gastrointestinal Agents (therapeutic use)
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic (genetics)
• Receptors, IgG (genetics)
• Treatment Outcome