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


CONCLUSIONS
Crohn's disease patients with FCGR3A-158 V/V genotype have a better biological and, possibly, clinical response to infliximab.
Department of Gastroenterology, CHU of Liège, Liège, Belgium.
E
E
Louis
Z
Z
El Ghoul
S
S
Vermeire
S
S
Dall'Ozzo
P
P
Rutgeerts
G
G
Paintaud
J
J
Belaiche
M
M
De Vos
A
A
Van Gossum
J-F
JF
Colombel
H
H
Watier
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D017452:Receptors, IgG; D000069285:Infliximab