Cartilage proteoglycan-induced arthritis in BALB/c mice. Antibodies that recognize human and mouse cartilage proteoglycan and can cause depletion of cartilage proteoglycan with little or no synovitis.
Human fetal cartilage proteoglycan (PG) induces the development of an erosive polyarthritis and spondylitis in BALB/c mice. We have examined the properties of 3 monoclonal antibodies (MAb) to human fetal cartilage PG isolated from immunized mice that cross-react with mouse cartilage PG. Compared with sera from arthritic mice, which contain antibodies reactive with keratan sulfate, MAb 202 (IgG1) reacted only with a protein-related epitope that is distributed on both hyaluronic acid-binding and chondroitin sulfate-attachment regions. MAb 813 (IgG1) reacted with the same fragments and recognized an epitope with the immunologic characteristics of keratan sulfate. MAb 945 (IgM) remains to be further characterized. Introduction of hybridomas secreting MAb 202 and MAb 945 into irradiated mice resulted in the loss of PG from articular cartilage and from growth plate cartilage (with MAb 202 only), as revealed by a loss of staining with toluidine blue. There was no synovial hyperplasia with MAb 202, but some hyperplasia and mononuclear cell infiltration was seen with MAb 945. This was accompanied by the binding of immunoglobulins to articular cartilage, as demonstrated by immunofluorescence. The hybridoma secreting MAb 813 produced no cartilage changes or synovitis, and there was no immunoglobulin binding to cartilage. Polymorphonuclear leukocyte infiltration was never observed with these antibodies. These studies indicate that MAb reactive with mouse cartilage PG can cause the depletion of PG from hyaline cartilage by mechanisms that may be both complement dependent and complement independent. Antibodies may serve to release and expose PG antigen to immune cells, as well as causing a loss of the mechanical properties of cartilage that are PG dependent.
Dayer
E
E
Joint Diseases Laboratory, Shriners Hospital for Crippled Children, Montreal, Quebec, Canada.
Mathai
L
L
Glant
T T
TT
Mikecz
K
K
Poole
A R
AR
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001168:Arthritis / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology*; D002356:Cartilage / Q000032:analysis; D002358:Cartilage, Articular / Q000032:analysis; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006132:Growth Plate / Q000032:analysis; D006801:Humans; D006825:Hybridomas / Q000166:cytology; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D010434:Pepsin A / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011509:Proteoglycans / Q000032:analysis / Q000276:immunology / Q000494:pharmacology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D010446:Peptide Fragments; D011509:Proteoglycans; D010434:Pepsin A