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Biomedical subjects

K Bleasdale

Publications and source records attributed to K Bleasdale.

7 recordsLinked to original sources
PubMed1989

Human thyroglobulin autoantibodies of subclasses IgG2 and IgG4 bind to different epitopes on thyroglobulin.

IgG autoantibodies to thyroglobulin (Tg) in the serum of patients with autoimmune thyroid disease only recognize a very limited number of epitopes, probably between four and six (Nye, Pontes De Carvalho & Roitt, 1980) on the large Tg molecule (660,000 MW), but attempts to characterize the epitopes have been unsuccessful so far (Male et al., 1985). The distribution of Tg autoantibodies between the IgG subclasses also tends to be restricted and individual patients possess characteristic 'fingerprints' of high affinity IgG1 and/or IgG4 Tg antibodies with smaller amounts of IgG2 Tg antibody (McLachlan et al., 1987, 1988). We have therefore investigated the possibility that Tg autoantibodies of different IgG subclasses interact with different epitopes on Tg.

Autoantibodies↗
PubMed1988

Determination of the functional affinity of IgG1 and IgG4 antibodies to tetanus toxoid by isotype-specific solid-phase assays.

Two solid-phase assays have been used to measure the affinity of IgG1 and IgG4 antibodies to tetanus toxoid (TT) in whole sera. In the first assay, low affinity antibodies were selectively inhibited from binding to solid-phase antigen by a mild chaotropic agent and in the second assay, high affinity antibodies were preferentially inhibited from binding by low concentrations of free antigen. Results from both assays suggest that IgG4 antibodies to TT are of lower functional affinity than IgG1 antibodies and that, in addition, IgG4 responses to TT display a more restricted affinity heterogeneity.

Antibodies, Bacterial↗
PubMed1987

Antibody affinity and IgG subclass of responses to tetanus toxoid in patients with rheumatoid arthritis and systemic lupus erythematosus.

Significant differences in both the affinity and IgG subclass of antibodies produced after immunization with tetanus toxoid have been demonstrated in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) compared to healthy controls. Patients with RA failed to show affinity maturation although they produced similar amounts of antibody to the controls. Some patients with SLE produced very high affinity antibodies although there was a wide spectrum of response. Antibodies to tetanus toxoid in controls were predominantly IgG1 and IgG4 but in RA and SLE there was either a restricted IgG1 response or a more general response in all the IgG subclasses. It is likely that these differences in response reflect the underlying disorders in immunoregulation present in patients with these diseases.

Adult↗
PubMed1984

Failure of affinity maturation leads to increased susceptibility to immune complex glomerulonephritis.

Mice, previously selected for the production of low affinity antibody after four injections of protein antigens in saline, fell into two groups on the basis of their antibody response after injection of adjuvantized antigen. One group produced antibody of sequentially rising affinity but the other produced only low affinity antibody. Mice from the latter group were interbred to produce low affinity non-maturing mice (low N/M mice). Daily injections in these mice produced a more rapid and severe glomerulonephritis than that observed in mice of the original low affinity line. Male low N/M mice were more severely affected than female low N/M mice. Susceptibility to the disease were associated not only with an inability to produce the maturational transition from low affinity to high affinity antibody with time but also with the production of low levels of antibody. It is suggested that these quantitative and qualitative defects in the antibody response may lead to increased susceptibility to immune complex disease.

Animals↗
PubMed1984

Antigen feeding modifies the course of antigen-induced immune complex disease.

Low affinity mice, prone to chronic immune complex disease (ICD) induced by daily injection of antigen, were fed 0.05% HSA in their drinking water for 7 days before the start of daily injections of HSA. Antigen feeding resulted in a marked decrease in the incidence of ICD despite the presence of high levels of circulating immune complexes. These complexes, which persisted in the circulation for long periods, were of low molecular weight and did not localize in the glomeruli. Antigen fed mice had lower levels of free antibody in their sera compared with control mice which may have favoured the formation of small latticed complexes in antigen excess. Antibody affinity was not apparently affected by prior feeding with antigen.

Administration, Oral↗
PubMed1982

Experimental antigen-antibody complex disease in mice. The role of antibody levels, antibody affinity and circulating antigen-antibody complexes.

Chronic antigen-antibody complex disease (A-ACD) was induced in mice by daily injections of HSA. The disease was characterized by death, intense glomerular basement membrane deposition of complexes in the kidneys, proteinuria and an impairment of the glomerular filtration rate. In mice that had been selectively bred to produce antibody of low affinity to protein antigens injected in saline, the incidence of chronic A-ACD was 61% compared to 21% in mice selectively bred to produce antibody of high affinity. Low affinity female mice produced approximately ten times as much free antibody to HSA as did low affinity males and high affinity males and females, but this did not result in an increase incidence of chronic A-ACD in low affinity female mice. Low affinity female mice also had the highest levels of circulating antigen-antibody complexes detected by conglutinin and Clq binding assays, but there was no correlation between the presence of high levels of complexes in serum and tissue damage. In both lines of mice the mean affinity of free antibody to HSA started low and increased with time and the number of injections of antigen. However, development of chronic A-ACD in individual low affinity mice appeared to be associated with a failure to produce this time-associated increase in antibody affinity. These results are discussed with reference to the relevance of the measurement of the amount of affinity of free antibody in serum and the levels of circulating antigen-antibody complexes to the production of tissue damage in this model of chronic A-ACD.

Animals↗