Demonstration of Cross-reacting Material in Tay-Sachs Disease

Overview

Journal Biochem J

Specialty Biochemistry

Date 1979 Jun 1

PMID 89845

Citations 3

Authors

S K Srivastava

N H Ansari

L A Hawkins

J E Wiktorowicz

Affiliations

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Abstract

Antibodies against placental hexosaminidase A and kidney alpha-subunits were raised in rabbits after cross-linking the antigens with glutaraldehyde. Anti-(alpha(n)-subunit) antiserum (anti-alpha(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-alpha(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) antiserum did not precipitate the CR material during the immunoelectrophoresis of Tay-Sachs liver extracts, it is suggested that altered alpha-subunits do not combine with beta-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 desease was found to be in the same range as theoretically calculated alpha-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.

Citing Articles

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PMID: 6852822 DOI: 10.1007/BF00284660.

Characterization of polypeptides serologically and structurally related to hexosaminidase in cultured fibroblasts.

Tsui F, Mahuran D, Lowden J, Mosmann T, Gravel R J Clin Invest. 1983; 71(4):965-73.

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Morquio's disease type A: absence of material cross reacting with antibodies against N-acetylgalactosamine-6-sulfate sulfatase.

Glossl J, Lembeck K, Gamse G, Kresse H Hum Genet. 1980; 54(1):87-91.

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