Interactions of synovial fluid immunoglobulins with chondrocytes.
OBJECTIVE
To study the interaction of synovial fluid (SF) immunoglobulins with living chondrocytes, and to evaluate the relative contribution of type II collagen (CII) antibodies.


METHODS
SF of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and gout were incubated with isolated bovine articular chondrocytes. Ig binding was measured by flow cytometry and by quantitation with 125I-labeled anti-IgG and anti-IgM. Complement-dependent cytotoxicity was determined by 51Cr release. Immunoglobulin binding and cytotoxicity were compared between chondrocytes obtained from the superficial and from the deep cartilage zones.


RESULTS
Significantly greater IgG and IgM binding was found with RA SF compared with OA or gout SF. Chondrocytes bound more Ig than did fibroblasts. The relative contribution of anti-CII antibodies to Ig binding was studied following absorption of the SF with bovine CII, and by incubation with bacterial collagenase-treated chondrocytes. There was a small but significant reduction in IgG and IgM binding with SF samples that were positive for anti-CII. RA SF exhibited modest, but significantly greater complement-dependent cytotoxicity than OA SF: Gel chromatography fractionation indicated that IgM antibodies were responsible for the cytotoxic activity. Additional studies showed that SF IgM antibodies bound preferentially to, and killed chondrocytes obtained from, the superficial layers of cartilage.


CONCLUSIONS
Anti-CII antibodies contained in RA SF represent one of many antibody specificities reacting with chondrocyte membrane antigens. Chondrocyte-reactive SF antibodies may play an important pathogenic role in the processes leading to irreversible cartilage damage in RA. These deleterious effects appear to be exerted particularly on chondrocytes located near the articular surface of cartilage.
Takagi
T
T
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Jasin
H E
HE
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D002358:Cartilage, Articular / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003094:Collagen / Q000032:analysis / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000378:metabolism; D007075:Immunoglobulin M / Q000032:analysis / Q000378:metabolism; D007136:Immunoglobulins / Q000032:analysis* / Q000378:metabolism; D007457:Iodine Radioisotopes; D011485:Protein Binding; D011863:Radioimmunoassay; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology*
D000906:Antibodies; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007457:Iodine Radioisotopes; D003094:Collagen