Clinical value of ELISA assays for IgM and IgG rheumatoid factors.

The clinical value of enzyme linked immunosorbent assays (ELISA) assays for IgM and IgG rheumatoid factors was assessed in a series of studies using rabbit IgG as antigen. The tests were reproducible with intra-assay coefficients of variation of 6% and could be simply and rapidly performed. Normal ranges were established using 106 sera from healthy controls. In a cross sectional study of 208 rheumatoid patients these assays were compared with the Rose-Waaler and laser nephelometric assessments of rheumatoid factor. In some patients there were discrepancies between rheumatoid factor positivity determined by one method or another. IgM ELISA and Rose-Waaler titres showed a significant correlation (r = +0.58; p less than 0.001), but there was a low correlation between IgM and IgG ELISA (r = +0.27; p less than 0.001). There was no evidence to show that the measurement of IgM or IgG rheumatoid factor gave significantly more clinical information than traditional tests such as the Rose-Waaler or latex agglutination tests.

Hereditary arthro-ophthalmopathy (Stickler syndrome): a diagnosis to consider in familial premature osteoarthritis.

A number of factors contribute to the pathogenesis of osteoarthritis. Genetic factors are predominant in some cases, including the syndrome of hereditary arthro-ophthalmopathy. The clinical features of the syndrome and the concept of genetic mutations in matrix components are discussed.

Differences between plasma and synovial fluid fibronectin.

Fibronectin is a high molecular weight glycoprotein of plasma and tissue fluids, and one of its functions is to opsonise particulate material. Chromatographic and electrophoretic analyses showed that the main components of fibronectin are biochemically similar in rheumatoid patients' plasma and synovial fluid. But synovial fluid fibronectin also contains a slow-moving component seen on two-dimensional immunoelectrophoresis, suggesting the presence of fibronectin complexes. Affinity chromatography provided evidence that these involved IgG, and in vitro studies showed that fibronectin influenced the reaction between IgG and anti-IgG. Synovial fluid fibronectin is functionally active in binding to gelatin in an haemagglutination assay, and it gave a relatively higher degree of haemagglutination than did plasma fibronectin, supporting the concept of multivalent fibronectin complexes in synovial fluid. These results suggest synovial fluid fibronectin may be involved in the opsonic removal of IgG-containing complexes from synovial fluid.

Low power laser therapy of shoulder tendonitis.

30 patients with supraspinatus or bicipital tendonitis were randomly allocated to active infrared laser therapy at 904 nm three times weekly for 2 weeks, dummy laser or drug treatment for 2 weeks. Objectively maximum active extension, flexion and abduction of the shoulder, and subjectively pain stiffness movement and function were measured at 0 and 2 weeks. Significant improvement of active over dummy laser was noted for all seven assessments. Active laser therapy produced significant improvement over drug therapy for all three objective measures and pain. Naproxen sodium significantly improved only movement and function compared to dummy laser. These results demonstrate the effectiveness of laser therapy in tendonitis of the shoulder.

Development of a new radiographic scoring system using digital image analysis.

A scoring system using computerised analysis of digital stored images of knee radiographs has been developed. Measurement is based on the assessment of joint space size. It is sensitive, rapid, and reproducible. Plain radiographs are positioned on an acetate grid; a computer generated grid is superimposed on a digital image of the radiograph viewed on a closed circuit television monitor and the joint space measured automatically. Area and distance have been assessed; area measurements are more reproducible. Application of microcomputer based digital image analysis to radiological scoring systems is an important step in understanding the nature and progression of arthritis.

Objective relief of vasospasm by glyceryl trinitrate in secondary Raynaud's phenomenon.

An objective response to topical glyceryl trinitrate was shown by digital plethysmography in a study of 17 patients with Raynaud's phenomenon. Improvement was significant (P less than 0.005) in those in whom the disease was secondary to an underlying connective tissue disorder. The response suggests that the effect of this drug is mediated locally.

Fibronectin in polyethylene glycol precipitates: evidence for a role in immune complexes.

Fibronectin is involved in the opsonic clearance of particulate material. It is present in plasma and synovial fluid and thus might be expected to have a role in the clearance of immune complexes. We have investigated this in a study of polyethylene glycol (PEG) precipitable material from the serum of patients with rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue disorders. Fibronectin is a significant component of PEG precipitates but the amount present is influenced by the method of preparation: more precipitates at 4 degrees C than at 20 degrees C. Fibronectin precipitation by PEG was considered to be related to immune complexes because: there was no direct relationship between serum fibronectin levels and the amount present in PEG precipitates; radiolabelled purified isolated fibronectin did not precipitate in 4% PEG; there was a direct relationship between the amount of fibronectin in PEG precipitates and the amounts of immunoglobulin G, A, and M. These results indicate that fibronectin is involved in immune complexes in rheumatic diseases, though they do not show it has an important biological role in these circumstances.

Fibronectin and immune complexes in rheumatic diseases.

The relation between fibronectin and immune complexes in rheumatic disease was examined in a series of linked studies. Fibronectin was present in immune complexes formed in vitro in the absence of C1q. Gel filtration chromatography showed complexed fibronectin was present in the serum of a patient with rheumatoid vasculitis, but not in normal serum; the complexed fibronectin coeluted with IgA and C3. Two dimensional immunoelectrophoresis showed a single fibronectin component was present in normal serum, but a number of components were present in serum from a rheumatoid patient. Polyacrylamide gel electrophoresis followed by immunoblotting for fibronectin showed that polyethylene glycol precipitates of synovial fluid contained immunoreactive components of a variety of sizes, indicating the presence of fragments of the molecule. An analysis of fibronectin in polyethylene glycol precipitates of paired serum and synovial fluid samples from 17 patients with rheumatoid arthritis and 16 with osteoarthritis showed more fibronectin was present in rheumatoid samples, especially in synovial fluid. More fibronectin was also present in synovial fluid than in serum polyethylene glycol precipitates; there was no direct relationship with C1q levels. All these results suggest that fibronectin is an integral component of immune complexes. This has potential pathogenic significance because it shows that a product of connective tissue cells may influence the functions of the immune system.

Individual variation in the isotype profile of anti-histone autoantibodies in systemic lupus erythematosus.

Using a solid-phase radioimmunoassay we have measured levels of anti-histone autoantibodies of the IgG, IgA and IgM heavy chain classes in 40 patients with systemic lupus erythematosus. Twenty-two patients (55%) had significantly elevated levels of at least one anti-histone isotype. Our results reveal four characteristics of the anti-histone response. (1) There is wide variation between patients in the isotype profile of anti-histone antibodies and these isotype profiles are a consistent individual characteristic. (2) There is no significant correlation between the level of IgG, IgA and IgM anti-histone in individual patients and a marked tendency for a single isotype (either IgG, IgA or IgM) to predominate in any one patient. (3) IgG anti-histone antibodies are predominantly of the IgG1 subclass. (4) Among 12 patients tested, IgG and IgA antibodies showed a preference for histones 1 and 2B whereas IgM antibodies showed no consistent preference for individual histones.

Enalapril in Raynaud's phenomenon.

The effect of enalapril in the treatment of Raynaud's phenomenon was assessed in a prospective double-blind cross-over trial in 17 patients (nine primary Raynaud's, eight Raynaud's associated with scleroderma). Each patient received 20 mg enalapril daily and placebo for 3 weeks with a 2-week washout period in between. The severity and frequency of Raynaud's attacks were measured subjectively by a diary count and objectively by measurement of finger systolic pressure changes in response to cooling (cold challenge test). Enalapril was associated with a reduction in the frequency of Raynaud's attacks, especially in patients with primary Raynaud's, compared with placebo, but there was no effect on the cold challenge test. We conclude that enalapril, like other vasodilator drugs, helps the symptoms of Raynaud's phenomenon, especially in patients with idiopathic or primary disease.

What proteins are present in polyethylene glycol precipitates from rheumatic sera?

The proteins present in 4% polyethylene glycol (PEG) precipitates of 10 normal sera and 60 samples from patients with rheumatic diseases were studied. A variety of immunochemical methods were used, including estimation of the percentages of total serum proteins precipitated by PEG, gel filtration analyses of the precipitates, and affinity chromatography with protein A and anti-immunoglobulin columns. Substantial amounts of protein were precipitated from normal sera. Many non-immunoglobulin proteins were precipitated from patients' sera, including fibronectin, haptoglobin, albumin, transferrin, and alpha 1-antitrypsin. Affinity chromatography with anti-immunoglobulin columns bound non-immunoglobulin proteins from PEG precipitates, but the protein A affinity column did not do so. The view that circulating antibody-antigen complexes alone are precipitated by 4% PEG is too simplistic; many non-immunoglobulin proteins are involved. They may either bind to immune complexes or be coprecipitated owing to non-specific protein aggregation.

Development and assessment of a computerized index of clinical disease activity in systemic lupus erythematosus. Members of the British Isles Lupus Assessment Group (BILAG).

Five centres in Great Britain and the Republic of Ireland have collaborated to produce a computerized index of clinical disease activity in systemic lupus erythematosus, based on the principle of the physician's intention to treat. The index assesses separately eight organ-based systems. The index has proved quick and easy to use despite a comprehensive database and compares favourably with two other indices of disease activity. It has great potential for use in multicentre studies of disease outcome and new therapies in systemic lupus erythematosus.

Enteric coated naproxen; a double blind trial comparing the tolerance of enteric coated and standard formulations.

Enteric coated naproxen (Nycopren) was compared with standard naproxen in a double blind comparative trial of 348 patients with either rheumatoid or osteoarthritis. There were slightly fewer gastric side effects and slightly fewer withdrawals because of side effects in the enteric coated naproxen group but the differences did not reach statistical significance. There was no significant difference in the efficacy of the two formulations. A satisfaction index was used to assess the therapeutic ratio with visual analogue scales assigned to both efficacy and side effects. The scale performed as intended and is worthy of further exploration.