HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The relative affinity of recombinant dihydrolipoamide transacetylase for autoantibodies in primary biliary cirrhosis.

Abstract
In normal individuals there is an adaptive immune response to a foreign antigen in which antibodies of increasing affinity are produced with time. This is not always true of an autoimmune response. However, because only a limited number of autoantigens have been cloned or purified, this issue has not been studied well. In primary biliary cirrhosis the predominant manifestation of autoimmunity is antimitochondrial antibodies that react with dihydrolipoamide transacetylase. The availability of recombinant dihydrolipoamide transacetylase and the development of a rapid and reproducible enzyme-linked immunosorbent assay for autoantibodies has allowed us to address the affinity of autoantibodies using thiocyanate inhibition. Thiocyanate is a chaotropic compound known to inhibit antigen-antibody binding in a concentration-dependent manner. We used this property to inhibit the binding by enzyme-linked immunosorbent assay of human recombinant dihydrolipoamide transacetylase with serum autoantibodies from 55 patients with primary biliary cirrhosis. The relative affinity and serum autoantibody titers were then compared with the histological stage of the liver biopsy sample. Interestingly, we found a considerable heterogeneity of relative affinities. These relative affinities did not correlate with the histological stage or the serum titer of antimitochondrial antibodies. However, the ability of serum autoantibodies to inhibit intact primary biliary cirrhosis enzyme activity was found to correlate highly (R2 = 0.751) with the relative affinity. Thus there are profound differences between patients with respect to qualitative expression of autoantibodies. The significance of this data will be unclear until more is determined regarding the nature of the epitope that drives T cells and leads to B-cell responses.
AuthorsC A Robertson, R L Coppel, T Prindiville, D Fregeau, M Kaplan, E R Dickson, M E Gershwin
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 11 Issue 5 Pg. 717-22 (May 1990) ISSN: 0270-9139 [Print] United States
PMID2347544 (Publication Type: Journal Article)
Chemical References
  • Autoantibodies
  • Pyruvate Dehydrogenase Complex
  • Recombinant Proteins
  • Thiocyanates
  • Acetyltransferases
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • thiocyanate
Topics
  • Acetyltransferases (immunology)
  • Antibody Affinity
  • Antigen-Antibody Reactions (drug effects)
  • Autoantibodies (immunology)
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • Humans
  • Liver Cirrhosis, Biliary (enzymology, immunology)
  • Pyruvate Dehydrogenase Complex
  • Recombinant Proteins
  • Thiocyanates (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: