Biomedical subjects

J B Marriott

Publications and source records attributed to J B Marriott.

21 records · Page 2Linked to original sources

PubMed1994

Serial functional affinity of autoantibodies in anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (GBM) disease is caused by an autoantibody directed against an epitope on the alpha 3 chain of type IV collagen. Animal models demonstrate that the higher the affinity of such antibodies, the greater the degree of glomerular injury. Affinity maturation (the process whereby somatic mutation followed by antigen selection leads to an increase in affinity of antibody) might therefore be of pathogenic significance if it occurs in human anti-GBM disease. We have examined serial samples from nine patients with anti-GBM disease and looked for evidence of changing functional affinity by measuring the inhibition of binding produced by the mild chaotrope diethylamine (DEA) in an anti-GBM antibody ELISA. Seven patients showed no change in the inhibition produced by DEA with time. Two patients showed an apparent decrease with time in the inhibition produced by DEA; this apparent increase in functional affinity proved, on further investigation, to represent simply the loss of anti-GBM antibodies. These results may imply that affinity maturation has been completed by the time that patients present with anti-GBM disease. If there had been evidence for a further increase in functional affinity after this point then this might have added extra urgency to the need for removal of these autoantibodies as part of treatment.

Antibody Affinity↗

PubMed1993

Antimitochondrial autoantibodies in anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (GBM) disease is characterized by the production of an autoantibody with very restricted specificity, with no evidence of polyclonal B cell activation. It was therefore surprising to find that in a solid-phase ELISA a proportion of anti-GBM sera showed significant binding to pyruvate dehydrogenase (PDH), a reactivity usually associated with the antimitochondrial autoantibodies (AMA) found in primary biliary cirrhosis (PBC). The specificity of this reactivity was confirmed by inhibition and competition experiments. The AMA found in anti-GBM sera were of much lower affinity than those found in PBC sera, and recognized a more restricted set of species (mainly the 55-kD and occasionally the 74-kD component of PDH). However, it was possible to block the binding in a Western blot of an anti-GBM serum to both the 55-kD and 74-kD species with F(ab')2 fragments prepared from a PBC serum. Although AMA have been found in diseases other than PBC, such diseases have usually been characterized by polyclonal B cell activation. The stimulus to the production of AMA in anti-GBM disease, and their significance in pathogenesis (if any), are unknown.

Autoantibodies↗

PubMedDate not supplied

The functional affinity and specificity of autoantibodies in animal models of anti-glomerular basement membrane disease.

We studied characteristics of the anti-glomerular basement membrane (GBM) antibody response in three animal models of Goodpasture's disease: treatment of Brown Norway (BN) rats with the polyclonal activator mercuric chloride (HgCl2), and immunization of BN and Wistar Kyoto (WKY) rats with rat GBM. Serial serum samples were obtained over the time course of the models, and anti-GBM antibodies eluted from the kidneys. Functional affinity of the anti-GBM antibodies was measured in a solid-phase ELISA incorporating the mild chaotropic agent diethylamine. Evidence for shared epitope specificity with human anti-GBM antibodies was sought using competition ELISA. As with recent studies in human anti-GBM disease, there was no evidence for affinity maturation of the anti-GBM response in the serum of any of the animal models. Antibodies eluted from the kidneys were of higher functional affinity than serum antibodies only in the HgCl2-treated BN rat. There was no obvious correlation between the functional affinity of the antibodies and the severity of nephritis in the three models. Competition studies between eluted anti-GBM antibodies from the rat models and human anti-GBM antibodies did not provide any evidence for shared epitope recognition. This study provides further information on the extent to which these models reflect the human disease.

Animals↗