C W Hutton

99mTc HMDP bone scanning in generalised nodal osteoarthritis. II. The four hour bone scan image predicts radiographic change.

In 14 patients with generalised nodal osteoarthritis a four hour bone scan image was found to predict the changes that occur on the radiograph at follow up between three and five years later. The scan abnormality appeared to precede the development of radiographic signs, and joints abnormal on scintigraphy showed most progression. Normal joints and joints abnormal on x ray alone showed little progression, and those that did subsequently alter became abnormal on scan. Scanning may provide a sensitive technique for monitoring osteoarthritis, it may enable a greater understanding of the underlying disease process, and allow evaluation of modifying therapeutic procedures.

Concentrations of glycosaminoglycans in synovial fluids and their relation with immunological and inflammatory mediators in rheumatoid arthritis.

The dimethylmethylene blue assay showed higher concentrations of glycosaminoglycans in many synovial fluids from patients with rheumatoid arthritis (RA) than in autologous sera or sera or synovial fluids from normal subjects. These results were taken to suggest that the glycosaminoglycans in RA synovial fluid were abnormally raised and derived from cartilage. To discover what stimulated such glycosaminoglycan release in RA joints relations were sought between synovial fluid concentrations of glycosaminoglycans and immunological and inflammatory mediators. It was shown that RA synovial fluid glycosaminoglycan concentrations correlated with synovial fluid C3d concentrations but not with synovial fluid rheumatoid factor concentrations, polymorphonuclear leucocyte numbers, myeloperoxidase concentrations, or the ability of the synovial fluids to release free radicals from normal polymorphonuclear leucocytes. A correlation was found between synovial fluid C3d and interleukin 1 concentrations as judged by both lymphocyte activating factor activity and immunoassay, but no significant correlation was detected between interleukin 1 and glycosaminoglycan concentrations. It is suggested that in the rheumatoid joint locally produced cytokines, in addition to interleukin 1, together stimulate glycosaminoglycan release from cartilage and render it vulnerable to attack by other processes.

Comparative study of C reactive protein and serum amyloid A protein in experimental inflammation.

The responses of C reactive protein, measured by radial immunodiffusion and radioimmunoassay, and serum amyloid A protein, measured by radial immunodiffusion, were compared in eight subjects with inflammation induced experimentally by intradermal injection of monosodium urate crystals. A significant increase in serum amyloid A was noted after a lag phase of eight hours, the increase in median concentration at 48 hours being about eightfold. A parallel but less marked increase was found in C reactive protein when measured by radioimmunoassay (fourfold increase in median concentration at 48 hours) after a small but significant decrease during the lag phase. The changes in C reactive protein remained within the reference range and were not detectable by radial immunodiffusion.

Isolation and analysis of complement activating aggregates from synovial fluid of patients with rheumatoid arthritis using monoclonal anti-C3d antibodies

The complement activating aggregates in synovial fluids of patients with rheumatoid arthritis (RA) have been isolated using monoclonal IgM anti-C3d antibodies attached to solid phases, and the content of the material bound has been analysed. High levels of aggregated IgG bearing C3d were found in RA synovial fluids, and IgG was the major immunoglobulin bound from such synovial fluids by anti-C3d Sepharose. A strong correlation was shown between levels of aggregated IgG bearing C3d and complement activation, as judged by C3d levels. Significant (but less strong) relationships were also observed between C3d levels and both complement consuming and C1q binding activity. C3d levels and levels of aggregated IgG bearing C3d were both significantly associated with the numbers of polymorphonuclear leucocytes (PMNs) found in RA synovial fluids. From these results it is concluded that the aggregated immunoglobulins bearing C3d (particularly IgG) isolated from RA synovial fluids are responsible for activating complement and attracting PMNs into the joint space. Radioimmunoassay showed no correlation, however, between levels of aggregated IgG (or IgM) bearing C3d and rheumatoid factor (RF) activity bound by anti-C3d. In addition, the material bound by anti-C3d Sepharose from most synovial fluid polyethylene glycol precipitates did not contain either IgM or IgG RF. Thus both techniques show that the majority of complexes bearing C3d do not contain RF. As the complement fixing aggregates apparently contain only immunoglobulin and complement components the results raise the problem of how the aggregates are formed. It is suggested that RA IgG may remain aggregated after either antigen or antibody (RF) has dissociated from the complex.

Systemic response to local urate crystal induced inflammation in man: a possible model to study the acute phase response.

The production of a systemic inflammatory response to intradermal monosodium urate crystal injection is described. A transient, self-limiting local response is associated with a systemic response detectable by a rise in the white cell count and serum amyloid A protein. The white cell change parallels the evolution of the local response, whereas the serum amyloid A response lags behind the local lesion, peaking after the local lesion is resolving. Intradermal monosodium urate injection is proposed as a possible inflammatory stimulus to explore the acute phase protein response in different disease states.

Mononuclear phagocytes in rheumatoid arthritis: Fc-receptor expression by peripheral blood monocytes.

Fc receptor expression by enriched monocytes from rheumatoid arthritis (RA) patients and age and sex matched controls (healthy subjects) was compared by measuring the uptake of IgG on monocytes in a competitive radioassay. The association constant (Ka) between IgG and the monocytes and the number of Fc binding sites per cell was calculated from Scatchard plots of 4 degrees C binding data. RA monocytes had increased expression of Fc receptors as compared with those of controls. This increase was particularly pronounced in those RA patients affected by extra-articular disease. There were significant correlations between the numbers of Fc receptors on monocytes and both C1q binding and anticomplementary activity but none between monocyte Fc receptor numbers and serum rheumatoid factors (IgG and IgM). It is considered that monocyte handling of circulating immune complexes is unimpaired in RA and that monocytes make an adaptive response to increased levels of immune complexes.