Demonstration of cross-reacting material in Tay-Sachs disease

S. K. Srivastava, N. H. Ansari, L. A. Hawkins, J. E. Wiktorowicz

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Antibodies against placental hexosaminidase A and kidney α-subunits were raised in rabbits after cross-linking the antigens with glutaraldehye. Anti-(α(n)-subunit) antiserum (anti-α(n)) precipitated hexosaminidase A but not hexosaminidase B, whereas anti-(hexosaminidase A) antiserum precipitated both hexosaminidases A and B. Specific anti-(hexosaminidase A) antiserum was prepared by absorbing antiserum with hexosaminidase B. Both anti-α(n) and anti-(hexosaminidase A) antisera precipitated the CR (cross-reacting) material from eight unrelated patients with Tay-Sachs disease. Immunotitration, immunoelectrophoresis, double-immunodiffusion and radial-immunodiffusion techniques were used to demonstrate the presence of CR material. The CR-material-antibody complex was enzymically inactive. Antiserum raised against kidney or placental hexosaminidase A, without cross-linking with glutaraldehyde, failed to precipitate the CR material, implying that treatment of the protein with glutaraldehyde exposes antigenic determinants that are hidden in the native protein. Since anti-(hexosaminidase B) anti-serum did not precipitate the CR material during the immunoelectrophoresis of Tay-Sachs liver extracts, it is suggested that altered α-subunits do not combine with β-subunits. By using immunotitration we have demonstrated the competition between the hexosaminidase B-free Tay-Sachs liver extract and hexosaminidase A for the common binding sites on monospecific anti-(cross-linked hexosaminidase A) antiserum. The amount of CR material in the liver samples from seven cases of Tay-Sachs disease was found to be in the same range as theoretically calculated α-subunits in normal liver samples. Similar results were obtained by the radial-immunodiffusion studies. The present studies therefore suggest that Tay-Sachs disease is caused by a structural-gene mutation.

Original languageEnglish (US)
Pages (from-to)657-664
Number of pages8
JournalBiochemical Journal
Volume179
Issue number3
DOIs
StatePublished - 1979

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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