Int J Med Sci 2018; 15(1):10-15. doi:10.7150/ijms.22812
A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF
1. Gastroenterology Department, Santa Lucía General University Hospital (HGUSL), C/ Mezquita sn, 30202 Cartagena, Spain;
2. Pathology Department, HGUSL, Cartagena, Spain;
3. Institute for Biohealth Research from Murcia (IMIB), Cartagena, Spain;
4. Clinical Analysis Department, HGUSL. Instituto Murciano de Investigaciones Biosanitarias (IMIB-Arrixaca), Murcia, Spain;
5. Pharmacy Department, HGUSL, Cartagena, Spain;
6. Faculty of Health Sciences. Catholic University from Murcia (UCAM), Murcia, Spain;
7. Statistical Unit, Fundación para la Formación e Investigación Sanitarias (FFIS), C/ Luis Fontes Pagán 9, 30003 Murcia, Spain.
Background. The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance. Material and Methods. A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured. Results. No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03). Conclusion. FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients.
Keywords: Crohn's Disease, ulcerative colitis, infliximab, adalimumab, anti-drug antibody, pharmacogenetics.
Romero-Cara P, Torres-Moreno D, Pedregosa J, Vílchez JA, García-Simón MS, Ruiz-Merino G, Morán-Sanchez S, Conesa-Zamora P. A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF. Int J Med Sci 2018; 15(1):10-15. doi:10.7150/ijms.22812. Available from http://www.medsci.org/v15p0010.htm