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Biomedical subjects

L Bevis

Publications and source records attributed to L Bevis.

6 recordsLinked to original sources

High levels of type 2 cytokine-producing cells in chronic fatigue syndrome.

The aetiology of chronic fatigue syndrome (CFS) is not known. However, it has been suggested that CFS may be associated with underlying immune activation resulting in a Th2-type response. We measured intracellular production of interferon (IFN)-gamma and interleukin (IL)-2; type 1 cytokines), IL-4 (type 2) and IL-10 (regulatory) by both polyclonally stimulated and non-stimulated CD4 and CD8 lymphocytes from patients with CFS and control subjects by flow cytometry. After polyclonal activation we found evidence of a significant bias towards Th2- and Tc2-type immune responses in CFS compared to controls. In contrast, levels of IFN-gamma, IL-2 and IL-10-producing cells were similar in both study groups. Non-stimulated cultures revealed significantly higher levels of T cells producing IFN-gamma or IL-4 in CFS patients. Concluding, we show evidence for an effector memory cell bias towards type 2 responsiveness in patients with CFS, as well as ongoing type 0 immune activation in unstimulated cultures of peripheral blood cells.

Adult↗

Alpha 1-antitrypsin deficiency, complement activation, and chronic liver disease.

Activation of the complement system, the main humoral mediator of inflammation, is restrained by the action of enzyme inhibitors including alpha 1-antitrypsin. Deficiency leads to chronic liver disease in about one in five children with this genetic defect. Complement activation was investigated in 34 children with alpha 1 AT deficiency (12 with minimal, 10 with moderate, and 12 with severe liver disease) and in 38 sex and age matched normal children by measuring the complement parent molecules C3, C4, the C3d fragment and by calculating the C3d:C3 ratio. C3 and C4 were lower in children with severe liver disease compared with controls, indicating impairment of hepatic protein synthesis or complement consumption. The C3d activation fragment was higher in all the patient groups when compared with controls while the C3d:C3 ratio, a measure of activation independent of the concentrations of the parent molecule, was higher in patients than in controls and increased with the degree of disease severity. These results suggest that complement may have a role in the pathogenesis of the chronic liver disease associated with alpha 1AT deficiency.

Adolescent↗

Double stranded DNA binding in autoimmune chronic active hepatitis and primary sclerosing cholangitis starting in childhood.

Autoimmune chronic active hepatitis (aCAH) and primary sclerosing cholangitis (PSC) are liver disorders occurring in childhood in which non-organ specific autoantibodies, such as anti-nuclear antibody (ANA) are frequently found. Antibodies to double stranded DNA (dsDNA), which are typically present in systemic lupus erythematosus (SLE), have been detected in both acute and chronic liver diseases in adults. In this study, using a radioimmunoassay technique widely employed to measure antibodies to dsDNA, we have demonstrated significantly increased levels (median and range; 11.9, 1.0-36.5 U/ml) in 21 children with aCAH compared with normal children (1.0, 0.7-2.1 U/ml; p less than 0.01). Five children with aCAH had levels in the range considered diagnostic for SLE (greater than 25 U/ml) and of these, three had ANA and two had anti-liver kidney microsomal antibody. In addition, one child had antibodies to dsDNA as detected by the Crithidia luciliae test. DNA binding in aCAH was correlated with serum aspartate-amino transferase levels (r = 0.68; p less than 0.001), suggesting a direct relationship with disease activity. In PSC, levels of antibodies to dsDNA were significantly increased compared to normal controls (median and range; 7.0, 5.6-10.2 U/ml; p less than 0.01) but were not as high as those found in aCAH.

Adolescent↗

Clinical application of a new nephelometric technique to measure complement activation.

A new nephelometric technique to measure C3d as an indicator of complement activation, is described. C3d is isolated at high concentration of polyethyleneglycol (PEG), incubated with commercially available anti-C3d antiserum at a final concentration of 2.5% PEG and then measured in a Behring Laser Nephelometer. In contrast to previously available techniques our assay detects the low concentrations of C3d present in all normal subjects, which result from the continuous C3 catabolism occurring in vivo. We have also measured C3d blood concentrations in a large number of patients with diseases associated with complement activation. Raised C3d concentrations were found in 68% of rheumatoid arthritis, 57% of primary biliary cirrhosis, 38% of chronic active hepatitis, 100% of Gram-negative bacteraemia and 100% of malaria. The nephelometric technique has proved to be sensitive, economical and fast, and could be adapted for routine determination of C3d blood concentrations to monitor disease activity and response to treatment.

Arthritis, Rheumatoid↗

Correlation in rheumatoid arthritis of concentrations of plasma C3d, serum rheumatoid factor, immune complexes and C-reactive protein with each other and with clinical features of disease activity.

The concentrations of C3d in the plasma and of C-reactive protein (CRP), immune complexes and rheumatoid factor in the serum were measured in 99 patients with rheumatoid arthritis. Most patients had raised levels, the values of which correlated with disease activity assessed according to a newly described index based on multivariate analysis of subjective, semi-objective and objective features of the disease. There were also significant correlations between the values for plasma C3d and circulating immune complexes, immune complexes and rheumatoid factor, serum CRP and immune complexes, and serum CRP and plasma C3d. Measurement of plasma C3d provides a useful means of detecting in vivo complement activation, which may be involved in the pathogenesis of rheumatoid arthritis, but neither C3d levels nor any of the other variables correlated as closely with disease activity as did the serum CRP concentration.

Adult↗