Biomedical subjects
Publications and source records attributed to R M Pope.
A patient with long-standing rheumatoid arthritis developed hyperviscosity syndrome that correlated with the presence of abundant intermediate complexes in plasma. The intermediate complexes were isolated, and evidence is presented that these complexes are composed predominantly of igG-rheumatoid factor.
The intermediate complexes, sedimenting between 19S and 6.6S components of normal serum on analytical ultracentrifugation, were purified from plasma of three patients with rheumatoid arthritis. Sequential gel filtration and removal of contaminants by agarose-antibody immunoadsorbents were employed for purification of these complexes. The isolated complexes from the three patients consisted of IgG with k and lambda light chains. Sedimentation equilibrium ultracentrifugation experiments showed that the isolated complexes underwent concentration-dependent self-association, whereby the smallest detectable molecular species had a molecular weight of 292,000. These IgG dimers were formed by self-association of IgG-rheumatoid factors, since nearly all F(ab) fragments, prepared from the isolated complexes by pepsin digestion, bound to normal IgG. The association constants for the interaction between normal IgG and one binding site of the F(ab) fragments were about 10-5 liters/mole. Since a cyclic structure with two antigen-antibody bonds was thought to form in the self-association of two IgG-rheumatoid factors, the association constant for dimer formation was calculated to be 10-10 liters/mole. The preferential self-association of IgG-rheumatoid factor was supported by the observation that monomeric normal human IgG did not replace the IgG-rheumatoid factor when the complexes were dissociated and reformed in the presence of excess normal IgG. The self-association of IgG-rheumatoid factors may be a general phenomenon in rheumatoid arthritis, as suggested by the observations of other investigators.
The serum and synovial fluid of many patients with rheumatoid arthritis contain immune complexes composed of immunoglobulin G (IgG). In this study such complexes from one patient are shown to be formed by self-association of IgG-antibodies to IgG (IgG-rheumatoid factors), so that each molecule serves as an antibody as well as an antigen. All F(ab')(2) and Fab' fragments derived from these complexes have antibody binding sites for normal IgG. Due to a high association constant in the formation of a cyclic complex by these antibodies, normal IgG is excluded as an antigen. These studies serve as a model for further elucidation of presence of similar immune complexes in the serum and synovial fluid of patients with rheumatoid arthritis.
Three patients with rheumatoid arthritis and abundant circulating intermediate complexes were studied. Two of these patients presented with the hyperviscosity syndrome. All 3 patients had markedly elevated plasma and blood viscosity, and the intermediate complexes were thought to be responsible for the increased viscosity. Studies on the isolated intermediate complexes revealed that they were formed by self-association of IgG-rheumatoid factors.
The clinical course of a patient is described who experienced respiratory insufficiency as the primary manifestation of immunoblastic lymphadenopathy. Respiratory symptoms preceded the enlargement of lymph nodes, improved spontaneously at first and then after steroid therapy. Subsequently these symptoms reappeared concurrent with lymph node enlargement. Hypergammaglobulinemia was noted with marked elevation of polyclonal immunoglobulin M.
The concentration of the acute phase serum protein C-reactive protein (CRP) is used as an index of disease activity in patients with rheumatoid arthritis and with other disorders associated with rheumatoid factor (RF). When CRP was determined by the latex agglutination method, RF caused both increased titers for CRP and false positive reactions for CRP. These effects of RF were abrogated by pretreatment of test samples with 2-mercaptoethanol. Detection of CRP by radial immunodiffusion was not affected by RF. Therefore, the clinical relevance of CRP detected in RF positive sera by latex agglutination can be ascertained only following pretreatment of sera with 2-mercaptoethanol or by the use of radial immunodiffusion to circumvent interference by RF.