Antibodies to native types I, 11, TX, and XI collagen were measured, using a 'L51-solid-phase radioimmunoassay, in serum from 104 patients with rheumatic diseases (rheumatoid arthritis, osteoporosis, Paget's disease, or osteoarthritis). In all disease groups, antibodies to type 11 collagen occurred with greater frequency than antibodies to type I collagen (1 1-3596 versus 5-23%). Antibodies to type XI collagen were the most frequent: They were present in -50% of the patients in the rheumatoid arthritis, Paget's disease, and osteoporosis groups. Antibodies to type IX collagen were found at a high frequency in the rheumatoid arthritis group only (44%). Analysis of the clinical data suggested that the presence of antibodies to collagen was associated with disease that was less severe or of shorter duration.
A pathogenic role of collagen autoimmunity in rheumatoid arthritis (RA) was first suggested based on the demonstration of collagen antibodies in patients' serum and synovial fluid (1,2). This hypothesis was later supported by the observation that native type I1 collagen, the major collagen component of cartilage, is arthritogenic when injected into rodents (3). Furthermore, this experimental arthritis is associated with both cellular and humoral immunity to type I1 collagen (4) and can be passively transferred with purified anticollagen IgG ( 5 ) . Subsequently, several reports indicated elevated serum levels of antibodies to types I and 11 collagen in a variety of rheumatic diseases, including RA ( 6 4 , relapsing polychondritis (9, lo), ankylosing spondylitis (9, I I ) , gout ( 6), juvenile rheumatoid arthritis (l2,13), systemic lupus erythematosus (14), and Dupuytren's disease (15).
Recently, new collagens in cartilage, types IX and XI ( l a , 2a, and 3a chains) collagen, called "minor collagens," have been described (16)(17)(18). Type IX collagen was demonstrated to be a potent immunogen in animals (l8,19), and type XI collagen, like type 11 collagen, appeared to be arthritogenic in rodents (20). We therefore investigated whether antibodies to these 2 collagens could also be implicated in rheumatic diseases in humans. We previously developed a solidphase radioimmunoassay (RIA) for the detection of serum IgG antibodies to various collagen types (21,22); this RIA was used to study patients with RA, osteoarthritis (OA), osteoporosis (OP), and Paget's disease (PD). The results obtained with types 1X and XI collagen were compared with those obtained with the more frequently studied types I and 11 collagen.