Exploring the binding sites of anti-infliximab antibodies in pediatric patients with rheumatic diseases treated with infliximab.
Over the past decade, the treatment of a variety of immune-mediated diseases has improved greatly due to the introduction of biologics for therapies in cases that are nonresponsive to traditional treatments. However, a side effect not encountered in traditional treatments is the immunogenicity of the biologics themselves. Our aim was to investigate the anti-infliximab-antibody response in pediatric patients receiving infliximab for juvenile idiopathic arthritis and other pediatric rheumatic diseases, with a focus on an analysis of the binding sites of these antibodies. We show that anti-infliximab antibodies developed in 43% of patients receiving infliximab therapy. Neutralization studies showed that in all these patients, the antibodies were directed toward the variable domains of infliximab, as they inhibited binding of infliximab to TNF. A more precise determination of the antibody epitopes using synthetic peptides was not achieved, indicating that all the antibody binding sites were composed of discontinuous segments of infliximab.
Department for Production of Diagnostic Reagents and Research, Blood Transfusion Centre of Slovenia, University of Ljubljana, SI-1000 Ljubljana, Slovenia. miha.kosmac@ztm.si
Miha
M
Kosmač
Tadej
T
Avčin
Nataša
N
Toplak
Gabriele
G
Simonini
Rolando
R
Cimaz
Vladka
V
Curin Šerbec
D000293:Adolescent; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000097:blood / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use*; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D000939:Epitopes; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D000069285:Infliximab; D011487:Protein Conformation; D012216:Rheumatic Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D000939:Epitopes; D007074:Immunoglobulin G; D000069285:Infliximab