title: Treatment with anti-NAP monoclonal antibody reduces disease severity in murine model of novel angiogenic protein-induced or ovalbumin-induced arthritis.
abstract: Rheumatoid arthritis (RA) is a polyarticular inflammatory, angiogenic disease. Synovial angiogenesis contributes to inflammation in RA. In this study we have developed an arthritic model in rats using a novel angiogenic protein (NAP), isolated from human synovial fluid of RA patients. We produced anti-NAP monoclonal antibodies (mAbs) and investigated the therapeutic efficacy of the same in adjuvant-induced or NAP-induced arthritis as a model of human RA. The treatment of arthritic rats with anti-NAP mAbs resulted in effective amelioration of paw oedema, radiological arthritic characteristics, serum levels of vascular endothelial growth factor (VEGF) and NAP, compared to that of untreated arthritic animals. Further, profiling of angiogenic markers such as synovial microvessel density, angiogenesis, CD31, VEGF and fms-like tyrosine kinase (Flt1) by immunohistochemistry both in arthritic and anti-NAP mAb-treated animals revealed the efficacy of mAb as an anti-angiogenic functional antibody. Therefore, NAP may be an attractive target to design anti-angiogenic and anti-arthritic therapies to control the pathogenesis of arthritis.
authors.affiliation: Department of Biotechnology, University of Mysore, Karnataka, India.
authors.forename: N B
authors.initials: NB
authors.lastname: Nataraj
authors.forename: J
authors.initials: J
authors.lastname: Krishnamurthy
authors.forename: B P
authors.initials: BP
authors.lastname: Salimath
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000276:immunology / Q000302:isolation & purification; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D002135:Calcium-Binding Proteins / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology
chemical_list: D043925:Angiogenesis Inducing Agents; D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D010047:Ovalbumin