Anticollagen antibodies and immune response gene products in rheumatoid arthritis

Abstract

Circulating antibodies to native and denatured types I and I1 human and bovine collagens were assayed in patients with rheumatoid arthritis (RA), patients with other rheumatic diseases, and normal individuals. A subgroup of this population was also assayed for reactivity with typing reagents which detect determinants (MT and HLA-DR) present in human immune response gene products. The mean titers of antibodies to each collagen tested were not significantly higher in RA patients when compared with patients who had other rheumatic diseases. Although both MT3 and MT4 were significantly associated with RA, there was no significant association between the anticollagen antibodies and any MT type or HLA-DR4. These studies raise a question concerning

Collagen antibodies in rheumatoid arthritis. SIgnificance of antibodies to denatured collagen and their association with HLA‐DR4

“…Since Steffen and Timpl (1) showed, in 1963, that the antibodies to homogenates of joint capsule cartilage from RA patients were reactive with collagen, many studies have confirmed that sera from patients with RA have antibodies to a variety of collagens (1)(2)(3)(4)(5)(6)(7)(8)(9). When tested, these antibodies have been found at higher titer in patients' synovial fluid as well (9-1 1).…”

“…These antibodies have been demonstrated to react to some degree with all types of collagen tested (9), but major interest has centered on type I collagen, which is found predominantly in skin, bone, vessels, and at joint surfaces, and type I1 collagen, which is found in hyaline cartilage. Antibodies have been shown to react with native collagens (M), denatured collagens (2), or both native and denatured collagens (3,8,9,11).…”

“…Protein A binds to IgG in human serum (although not to IgG3, which is 1-3% of total human IgG), and binds only slightly to IgM (12). IgG antibodies were chosen for study because of the good correlation between levels of IgG and IgM antibodies to native collagen in rheumatoid arthritis, demonstrated by Clague et a1 (6).Since normal human serum contains apparent anticollagen reactivity (1,4,7,8), we determined whether the serum reactivity in patients with RA differed qualitatively and/or quantitatively from that in normal subjects. Also, since HLA-DR4 is a major risk factor for RA (13), we correlated the presence of HLA-DR4 and associated haplotypes with levels of antibody to denatured and native type I1 collagen.…”

“…Studies conducted during the past several years have demonstrated the presence of antibodies to collagen in the serum (1)(2)(3)(4)(5)(6)(7)(8)(9) and synovial fluid (9-1 1) of patients with rheumatoid arthritis (RA), although it has not been possible to relate the presence or titer of collagen antibody to the course or severity of the disease. These studies have used a variety of collagen types as antigen, and often no distinction has been made between antibodies to native collagen and antibodies to denatured collagen.…”

“…Since normal human serum contains apparent anticollagen reactivity (1,4,7,8), we determined whether the serum reactivity in patients with RA differed qualitatively and/or quantitatively from that in normal subjects. Also, since HLA-DR4 is a major risk factor for RA (13), we correlated the presence of HLA-DR4 and associated haplotypes with levels of antibody to denatured and native type I1 collagen.…”