학술논문
Efficacy of an immunotoxin to folate receptor beta in the intra-articular treatment of antigen-induced arthritis
Document Type
Report
Source
Arthritis Research & Therapy. May 2, 2012, Vol. 14 Issue 3
Subject
Language
English
ISSN
1478-6354
Abstract
Author(s): Taku Nagai[sup.1] , Akira Kyo[sup.1] , Kazuhisa Hasui[sup.1] , Sonshin Takao[sup.2] and Takami Matsuyama[sup.1] Introduction Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease characterized by synovial hyperplasia and [...]
Introduction We previously demonstrated that synovial sublining macrophages express folate receptor beta (FR[beta]). The aim of this study was to evaluate the efficacy of intra-articular administration of a recombinant immunotoxin to FR[beta] for treating rat antigen-induced arthritis. Methods A monoclonal antibody (mAb) to rat FR[beta] was produced by immunizing mice with B300-19 cells (murine pre-B cells) transfected with the rat FR[beta] gene. Recombinant immunotoxin was prepared by conjugating the Fv portion of the anti-rat FR[beta] mAb heavy chain with a truncated Pseudomonas exotoxin A and the Fv portion of the anti-rat FR[beta] mAb light chain. Antigen-induced arthritis was induced through intra-articular injection of methylated bovine serum albumin (mBSA) after two subcutaneous injections of mBSA and complete Freund's adjuvant. Immunotoxin was intra-articularly injected into the arthritis joint every other day for seven days after arthritis onset. Joint swelling was measured and histological scores of inflammation, synovial thickness, cartilage, and bone destruction were determined. Immunohistochemistry was performed to detect osteoclast and osteoclast precursor FR[beta]-expressing macrophages and cathepsin K-positive cells on day 21. Results Intra-articular administration of the immunotoxin attenuated joint swelling (61% suppression; P < 0.01 compared to the control on day 21) and improved histological findings, particularly cartilage and bone destruction (scores of rats treated with control versus the immunotoxin: 2.2 versus 0.5; P < 0.01), by reducing the number of FR[beta]-expressing macrophages and cathepsin K-positive cells. Conclusions Intra-articular administration of an immunotoxin to FR[beta] is effective for improving rat antigen-induced arthritis.
Introduction We previously demonstrated that synovial sublining macrophages express folate receptor beta (FR[beta]). The aim of this study was to evaluate the efficacy of intra-articular administration of a recombinant immunotoxin to FR[beta] for treating rat antigen-induced arthritis. Methods A monoclonal antibody (mAb) to rat FR[beta] was produced by immunizing mice with B300-19 cells (murine pre-B cells) transfected with the rat FR[beta] gene. Recombinant immunotoxin was prepared by conjugating the Fv portion of the anti-rat FR[beta] mAb heavy chain with a truncated Pseudomonas exotoxin A and the Fv portion of the anti-rat FR[beta] mAb light chain. Antigen-induced arthritis was induced through intra-articular injection of methylated bovine serum albumin (mBSA) after two subcutaneous injections of mBSA and complete Freund's adjuvant. Immunotoxin was intra-articularly injected into the arthritis joint every other day for seven days after arthritis onset. Joint swelling was measured and histological scores of inflammation, synovial thickness, cartilage, and bone destruction were determined. Immunohistochemistry was performed to detect osteoclast and osteoclast precursor FR[beta]-expressing macrophages and cathepsin K-positive cells on day 21. Results Intra-articular administration of the immunotoxin attenuated joint swelling (61% suppression; P < 0.01 compared to the control on day 21) and improved histological findings, particularly cartilage and bone destruction (scores of rats treated with control versus the immunotoxin: 2.2 versus 0.5; P < 0.01), by reducing the number of FR[beta]-expressing macrophages and cathepsin K-positive cells. Conclusions Intra-articular administration of an immunotoxin to FR[beta] is effective for improving rat antigen-induced arthritis.