The degradation of type II collagen in rheumatoid arthritis: an immunoelectron microscopic study.
Rabbit antibodies were prepared that react only with denatured type II collagen alpha-chains and cleavage products. The epitopes that these antibodies recognize reside in cyanogen bromide peptides CB8 and CB11. The antibodies do not react with triple helical collagen nor with any other collagen or protein present in hyaline cartilage (Dodge and Poole, J. Clin. Invest. 83:647-661, 1989). These antibodies can therefore be used to detect denatured type II collagen produced, for example, by enzymatic cleavage. In this study they were used to determine, at the ultrastructural level, using immunogold staining, type II collagen fibril cleavage in articular cartilages remote from synovium and pannus of patients with rheumatoid arthritis. Comparisons were made with site- and age-matched healthy articular cartilages. Antibody binding was detected in the extracellular matrix, at the articular surface and in the deep zone, usually on visibly damaged collagen fibrils which exhibited a loss of the normal banding pattern of staining produced by lead citrate and uranyl acetate: binding was also observed in disrupted fibrils, sometimes at their ends. Binding was commonly associated with amorphous-looking material (and occasionally unstained sites) in the extracellular matrix which, because of the specificity of the antibody, can be identified as containing denatured or fragmented type II collagen, stained (and unstained) with heavy metals. In both rheumatoid and healthy articular cartilages, there was no antibody binding to intact well stained fibrils which exhibited a regular banding pattern. Little or no staining was detected at the ultrastructural level in normal cartilages.(ABSTRACT TRUNCATED AT 250 WORDS)
Dodge
G R
GR
Shriners Hospital for Crippled Children, Department of Surgery, McGill University, Montreal, Quebec, Canada.
Pidoux
I
I
Poole
A R
AR
D000328:Adult; D000906:Antibodies / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D016253:Microscopy, Immunoelectron; D008875:Middle Aged
D000906:Antibodies; D003094:Collagen