Demonstration of cross-reacting material in Tay-Sachs disease

Satish Srivastava, Naseem Ansari, L. A. Hawkins, J. E. Wiktorowicz

Research output: Contribution to journalArticle

5 Citations (Scopus)

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
StatePublished - 1979

Fingerprint

Hexosaminidase A
Tay-Sachs Disease
Hexosaminidase B
Demonstrations
Immune Sera
Immunodiffusion
Liver Extracts
Immunoelectrophoresis
Glutaral
Liver
Precipitates
Kidney
Antibodies
Epitopes
Proteins
Genes
Binding Sites
Rabbits

ASJC Scopus subject areas

  • Biochemistry

Cite this

Srivastava, S., Ansari, N., Hawkins, L. A., & Wiktorowicz, J. E. (1979). Demonstration of cross-reacting material in Tay-Sachs disease. Biochemical Journal, 179(3), 657-664.

Demonstration of cross-reacting material in Tay-Sachs disease. / Srivastava, Satish; Ansari, Naseem; Hawkins, L. A.; Wiktorowicz, J. E.

In: Biochemical Journal, Vol. 179, No. 3, 1979, p. 657-664.

Research output: Contribution to journalArticle

Srivastava, S, Ansari, N, Hawkins, LA & Wiktorowicz, JE 1979, 'Demonstration of cross-reacting material in Tay-Sachs disease', Biochemical Journal, vol. 179, no. 3, pp. 657-664.
Srivastava S, Ansari N, Hawkins LA, Wiktorowicz JE. Demonstration of cross-reacting material in Tay-Sachs disease. Biochemical Journal. 1979;179(3):657-664.
Srivastava, Satish ; Ansari, Naseem ; Hawkins, L. A. ; Wiktorowicz, J. E. / Demonstration of cross-reacting material in Tay-Sachs disease. In: Biochemical Journal. 1979 ; Vol. 179, No. 3. pp. 657-664.
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