Induced production of anti-etanercept antibody in collagen-induced arthritis.
Etanercept is a widespread biological drug for the treatment of rheumatoid arthritis, which inhibits tumor necrosis factor-α (TNF-α). Recently, the presence of antibodies targeting TNF-α inhibitors such as infliximab and adalimumab, was reported. However, few reports have studied etanercept in a mouse model of arthritis. We investigated the induction of anti-etanercept antibody production, along with the antibody's potential interfering effects on the biological function of etanercept, in mice with collagen-induced arthritis (CIA). CIA mice received an intraperitoneal injection of etanercept (25, 100 or 400 µg per mouse). The degree of inflammation and cartilage erosion was evaluated, and the number of osteoclasts in the ankle joints was assessed by TRAP staining. The level of pro-inflammatory cytokines in the serum was measured. To analyze the anti-osteoporotic effect of etanercept, microfocal computed tomography analyses of femurs and tibias were performed. Etanercept treatment decreased both the incidence and severity of arthritis in a dose-dependent manner, except for the highest dose of 400 µg. The mice that were treated with 25 and 100 µg etanercept showed an improvement in inflammation, cartilage damage, and even bone loss. However, mice treated with 400 µg etanercept showed no significant improvement in any of the tested parameters. Using a customized enzyme-linked immunosorbent assay (ELISA), the presence of the anti-etanercept antibody was detected in the serum in this treatment-refractory group. The therapeutic effect of etanercept was reduced in the CIA mice that developed the anti-etanercept antibody. In conclusion, the production of an anti-etanercept antibody can be induced in CIA mice, and this antibody can considerably reduce the anti-arthritic and anti-osteoporotic effects of etanercept.
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Hyoju
H
Yi
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Juryun
J
Kim
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Hyerin
H
Jung
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Yeri Alice
YA
Rim
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Youngkyun
Y
Kim
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Seung Min
SM
Jung
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Sung-Hwan
SH
Park
Division of Rheumatology, Department of Internal Medicine, CiSTEM Laboratory, Convergent Research Consortium for Immunological Disease (CRCID), Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Ji Hyeon
JH
Ju
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D018488:Bone Demineralization, Pathologic / Q000188:drug therapy; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D000068800:Etanercept; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000276:immunology*
D000906:Antibodies; D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept