Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1977 Jan;59(1):97–105. doi: 10.1172/JCI108627

Human beta-glucuronidase deficiency mucopolysaccharidosis: identification of cross-reactive antigen in cultured fibroblasts of deficient patients by enzyme immunoassay.

C E Bell Jr, W S Sly, F E Brot
PMCID: PMC333336  PMID: 401508

Abstract

An enzyme immunoassay for human beta-glucuronidase was developed to determine the presence or absence of antigenically cross-reactive material (CRM) in patients with beta-glucuronidase deficiency mucopolysaccharidosis. This assay provided a sensitive means of measuring the primary interaction between the enzyme molecule and antibody but required neither pure antigen nor monospecific antiserum, an important consideration, since neither of these was available. Goat antiserum to partially purified human placenta beta-glucuronidase did not recognize differences in normal enzyme from human placenta, liver, fibroblasts, or blood platelets. CRM was identified in fibroblast extracts from all four of the unrelated beta-glucuronidase-deficient patients studied, but titration patterns indicated genetic heterogeneity among these four mutant proteins. Fibroblast enzymes from two obligate heterozygotes were distinguishable immunologically from normal enzyme. The enzyme immunoassay was also used to compare human enzyme with liver enzyme from other mammalian species. CRM was present in liver extracts of all species tested, but the liver enzymes, except for the rabbit, were weakly cross-reactive. We conclude that despite certain limitations, the enzyme immunoassay for human beta-glucuronidase is useful and that all four beta-glucuronidase-deficient patients studied possess CRM.

Full text

PDF
97

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beaudet A. L., DiFerrante N. M., Ferry G. D., Nichols B. L., Jr, Mullins C. E. Variation in the phenotypic expression of beta-glucuronidase deficiency. J Pediatr. 1975 Mar;86(3):388–394. doi: 10.1016/s0022-3476(75)80968-1. [DOI] [PubMed] [Google Scholar]
  2. Boyer S. H., Siggers D. C., Krueger L. J. Caveat to protein replacement therapy for genetic disease. Immunological implications of accurate molecular diagnosis. Lancet. 1973 Sep 22;2(7830):654–659. doi: 10.1016/s0140-6736(73)92489-6. [DOI] [PubMed] [Google Scholar]
  3. Brady R. O., Pentchev P. G., Gal A. E., Hibbert S. R., Dekaban A. S. Replacement therapy for inherited enzyme deficiency. Use of purified glucocerebrosidase in Gaucher's disease. N Engl J Med. 1974 Nov 7;291(19):989–993. doi: 10.1056/NEJM197411072911901. [DOI] [PubMed] [Google Scholar]
  4. Brady R. O., Tallman J. F., Johnson W. G., Gal A. E., Leahy W. R., Quirk J. M., Dekaban A. S. Replacement therapy for inherited enzyme deficiency. Use of purified ceramidetrihexosidase in Fabry's disease. N Engl J Med. 1973 Jul 5;289(1):9–14. doi: 10.1056/NEJM197307052890103. [DOI] [PubMed] [Google Scholar]
  5. Brot F. E., Glaser J. H., Roozen K. J., Sly W. S., Stahl P. D. In vitro correction of deficient human fibroblasts by beta-glucuronidase from different human sources. Biochem Biophys Res Commun. 1974 Mar 15;57(1):1–8. doi: 10.1016/s0006-291x(74)80349-9. [DOI] [PubMed] [Google Scholar]
  6. Danes B. S., Degnan M. Chondroitin-6-sulfate mucopolysaccharidosis in conjuntion withlymphopenia, defective cellular immunity and the nephrotic syndrome. Birth Defects Orig Artic Ser. 1974;10(12):251–257. [PubMed] [Google Scholar]
  7. Dean M. F., Muir H., Benson P. F. Mobilization of glycosaminoglycans by plasma infusion in mucopolysaccharidosis type 3--two types of response. Nat New Biol. 1973 May 30;243(126):143–146. doi: 10.1038/newbio243143a0. [DOI] [PubMed] [Google Scholar]
  8. Gehler J., Cantz M., Tolksdorf M., Spranger J., Gilbert E., Drube H. Mucopolysaccharidosis. VII. Beta-glucuronidase deficiency. Humangenetik. 1974 Jul 15;23(2):149–158. doi: 10.1007/BF00282212. [DOI] [PubMed] [Google Scholar]
  9. Glaser J. H., Roozen K. J., Brot F. E., Sly W. S. Multiple isoelectric and recognition forms of human beta-glucuronidase activity. Arch Biochem Biophys. 1975 Feb;166(2):536–542. doi: 10.1016/0003-9861(75)90417-8. [DOI] [PubMed] [Google Scholar]
  10. Glaser J. H., Sly W. S. Beta-glucuronidase deficiency mucopolysaccharidosis: methods for enzymatic diagnosis. J Lab Clin Med. 1973 Dec;82(6):969–977. [PubMed] [Google Scholar]
  11. HAYASHI M., NAKAJIMA Y., FISHMAN W. H. THE CYTOLOGIC DEMONSTRATION OF BETA-GLUCURONIDASE EMPLOYING NAPHTHOL AS-BI GLUCURONIDE AND HEXAZONIUM PARAROSANILIN; A PRELIMINARY REPORT. J Histochem Cytochem. 1964 Apr;12:293–297. doi: 10.1177/12.4.293. [DOI] [PubMed] [Google Scholar]
  12. Hall C. W., Cantz M., Neufeld E. F. A -glucuronidase deficiency mucopolysaccharidosis: studies in cultured fibroblasts. Arch Biochem Biophys. 1973 Mar;155(1):32–38. doi: 10.1016/s0003-9861(73)80006-2. [DOI] [PubMed] [Google Scholar]
  13. Krivit W., Desnick R. J., Mapes C., Anderson R. L., Sweeley C. C. Recent advances in Fabry's disease. Trans Assoc Am Physicians. 1970;83:121–132. [PubMed] [Google Scholar]
  14. Neuwelt E., Kohler P. F., Austin J. Primary enzyme immunoassay (PEIA): studies of the mutant enzyme in metachromatic leukodystrophy (primary enzyme immunoassay of arylsulfatase-A). Immunochemistry. 1973 Nov;10(11):767–773. doi: 10.1016/0019-2791(73)90179-1. [DOI] [PubMed] [Google Scholar]
  15. O'Brien J. S., Miller A. L., Loverde A. W., Veath M. L. Sanfilippo disease type B: enzyme replacement and metabolic correction in cultured fibroblasts. Science. 1973 Aug 24;181(4101):753–755. doi: 10.1126/science.181.4101.753. [DOI] [PubMed] [Google Scholar]
  16. Sly W. S., Quinton B. A., McAlister W. H., Rimoin D. L. Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis. J Pediatr. 1973 Feb;82(2):249–257. doi: 10.1016/s0022-3476(73)80162-3. [DOI] [PubMed] [Google Scholar]
  17. Stahl P. D., Touster O. Beta-glucuronidase of rat liver lysosomes. Purification, properties, subunits. J Biol Chem. 1971 Sep 10;246(17):5398–5406. [PubMed] [Google Scholar]
  18. Swank R. T., Paigen K. Biochemical and genetic evidence for a macromolecular -glucuronidase complex in microsomal membranes. J Mol Biol. 1973 Jul 5;77(3):371–389. doi: 10.1016/0022-2836(73)90445-2. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES