Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1979 Jun;36(3):355–363.

Immunological and purine enzyme studies on hyperuricaemic and normouricaemic patients with Down's syndrome.

R W Watts, Y S Perera, J Allsop, C Newton, T A Platts-Mills, A D Webster
PMCID: PMC1537749  PMID: 158448

Abstract

Hyperuricaemia in Down's syndrome is unreleated to the activity of phosphoribosylamidotransfrease, which catalyses the activity of the first specific step on the purine biosynthetic pathway, and to the activity of hypoxanthine phosphoribosyltransferase and phosphoribosylpyrophosphate synthetase, abnormalities of which are known to be associated with hyperuricaemia. Immunological studies involving serum immunoglobulins, natural E. coli antibodies, test immunization with pneumococcal polysaccharide type III (PnPS), in vitro lymphocyte transformation to mitogens, and pokeweed mitogen (PWM) induced immunoglobulin production showed no difference between hyperuricaemic or normouricaemic Down's patients and institutionalized controls. The Down's patients had higher serum IgA, IgG and IgE, and some also produced more immunoglobulin in PWM-stimulated lymphocyte cultures when compared to normal healthy controls. However, both patients with Down's syndrome and the institutionalized controls had significantly lower responses to PnPs than normal healthy controls. The only deficiency confined to the Down's patients was a signficant depression in delayed hypersensitivity to dinitrochlorobenzene. These findings indicate that the in vivo abnormality of depressed cellular and humoral immunity in Down's patients is not paralleled by in vitro function as measured by PHA lymphocyte transformation and immunoglobulin production by PWM-stimulated lymphocytes. There is also no apparent link between a putative defect in purine metabolism in Down's patients and any immunological abnormalities.

Full text

PDF
355

Selected References

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

  1. Allison A. C., Hovi T., Watts R. W., Webster A. D. Immunological observations on patients with Lesch-Nyhan syndrome, and on the role of de-novo purine synthesis in lymphocyte transformation. Lancet. 1975 Dec 13;2(7946):1179–1183. doi: 10.1016/s0140-6736(75)92661-6. [DOI] [PubMed] [Google Scholar]
  2. Baker P. J., Stashak P. W., Prescott B. Use of erythrocytes sensitized with purified pneumococcal polysaccharides for the assay of antibody and antibody-producing cells. Appl Microbiol. 1969 Mar;17(3):422–426. doi: 10.1128/am.17.3.422-426.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Becker M. A., Meyer L. J., Wood A. W., Seegmiller J. E. Purine overproduction in man associated with increased phosphoribosylpyrophosphate synthetase activity. Science. 1973 Mar 16;179(4078):1123–1126. doi: 10.1126/science.179.4078.1123. [DOI] [PubMed] [Google Scholar]
  4. Coburn S. P., Seidenberg M., Mertz E. T. Clearance of uric acid, urea, and creatinine in Down's syndrome. J Appl Physiol. 1967 Oct;23(4):579–580. doi: 10.1152/jappl.1967.23.4.579. [DOI] [PubMed] [Google Scholar]
  5. Coburn S. P., Sirlin E. M., Mertz E. T. Metabolism of N15 labeled uric acid in Down's syndrome. Metabolism. 1968 Jun;17(6):560–562. doi: 10.1016/0026-0495(68)90049-8. [DOI] [PubMed] [Google Scholar]
  6. Craft J. A., Dean B. M., Watts R. W., Westwick W. J. Studies on human erythrocyte IMP: pyrophosphate phosphoribosyltransferase. Eur J Biochem. 1970 Aug;15(2):367–373. doi: 10.1111/j.1432-1033.1970.tb01017.x. [DOI] [PubMed] [Google Scholar]
  7. Dean B. M., Watts R. W.E., Westwick W. J. Human erythrocyte AMP: Pyrophosphate phosphoribosyltransferase (EC 2.4.2.7). FEBS Lett. 1968 Aug;1(3):179–182. doi: 10.1016/0014-5793(68)80054-7. [DOI] [PubMed] [Google Scholar]
  8. Gordon R. B., Thompson L., Emmerson B. T. Erythrocyte phosphoribosylpyrophosphate concentrations in heterozygotes for hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism. 1974 Oct;23(10):921–927. doi: 10.1016/0026-0495(74)90041-9. [DOI] [PubMed] [Google Scholar]
  9. Hawkes R. A., Boughton C. R., Schroeter D. R. The antibody response of institutionalized Down's syndrome patients to seven microbial antigens. Clin Exp Immunol. 1978 Feb;31(2):298–304. [PMC free article] [PubMed] [Google Scholar]
  10. Hollingsworth D. R., Hollingsworth J. W., Roeckel I., McKean H. E., Holland N. Immunologic reactions and Australia antigenemia in Down's syndrome. J Chronic Dis. 1974 Nov;27(9-10):483–490. doi: 10.1016/0021-9681(74)90041-1. [DOI] [PubMed] [Google Scholar]
  11. Howell A., Mason A. S., Brown E., Watts R. W., Chanarin I., McPherson K., Ridler M. A. Red cell size and uric acid in Down's syndrome. Scand J Haematol. 1973;11(2):140–147. doi: 10.1111/j.1600-0609.1973.tb00108.x. [DOI] [PubMed] [Google Scholar]
  12. Kaufman J. M., O'Brien W. M. Hyperuricemia in mongolism. N Engl J Med. 1967 Apr 27;276(17):953–956. doi: 10.1056/NEJM196704272761704. [DOI] [PubMed] [Google Scholar]
  13. Krenitsky T. A., Papaioannou R., Elion G. B. Human hypoxanthine phosphoribosyltransferase. I. Purification, properties, and specificity. J Biol Chem. 1969 Mar 10;244(5):1263–1270. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Levin S., Nir E., Mogilner B. M. T system immune-deficiency in Down's syndrome. Pediatrics. 1975 Jul;56(1):123–126. [PubMed] [Google Scholar]
  16. Lopez V., Ochs H. D., Thuline H. C., Davis S. D., Wedgwood R. J. Defective antibody response to bacteriophage phichi 174 in Down syndrome. J Pediatr. 1975 Feb;86(2):207–211. doi: 10.1016/s0022-3476(75)80469-0. [DOI] [PubMed] [Google Scholar]
  17. Pant S. S., Moser H. W., Krane S. M. Hyperuricemia in Down's syndrome. J Clin Endocrinol Metab. 1968 Apr;28(4):472–478. doi: 10.1210/jcem-28-4-472. [DOI] [PubMed] [Google Scholar]
  18. Platts-Mills T. A., Ishizaka K. IgA and IgA diphtheria antitoxin responses from human tonsil lymphocytes. J Immunol. 1975 Mar;114(3):1058–1064. [PubMed] [Google Scholar]
  19. Seegmiller J. E., Rosenbloom F. M., Kelley W. N. Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science. 1967 Mar 31;155(3770):1682–1684. doi: 10.1126/science.155.3770.1682. [DOI] [PubMed] [Google Scholar]
  20. Sperling O., Eilam G., Sara-Persky-Brosh, De Vries A. Accelerated erythrocyte 5-phosphoribosyl-1-pyrophosphate synthesis. A familial abnormality associated with excessive uric acid production and gout. Biochem Med. 1972 Aug;6(4):310–316. doi: 10.1016/0006-2944(72)90017-8. [DOI] [PubMed] [Google Scholar]
  21. Stiehm E. R., Fudenberg H. H. Serum levels of immune globulins in health and disease: a survey. Pediatrics. 1966 May;37(5):715–727. [PubMed] [Google Scholar]
  22. Van Acker K. J., Simmonds H. A., Potter C., Cameron J. S. Complete deficiency of adenine phosphoribosyltransferase. Report of a family. N Engl J Med. 1977 Jul 21;297(3):127–132. doi: 10.1056/NEJM197707212970302. [DOI] [PubMed] [Google Scholar]
  23. Watts R. W. Uric acid biosynthesis and its disorders. J R Coll Physicians Lond. 1976 Oct;11(1):91–106. [PMC free article] [PubMed] [Google Scholar]
  24. Webster A. D., Efter T., Asherson G. L. Escherichia coli antibody: a screening test for immunodeficiency. Br Med J. 1974 Jul 6;3(5922):16–18. doi: 10.1136/bmj.3.5922.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wood A. W., Seegmiller J. E. Properties of 5-phosphoribosyl-1-pyrophosphate amidotransferase from human lymphoblasts. J Biol Chem. 1973 Jan 10;248(1):138–143. [PubMed] [Google Scholar]
  26. Wu L. Y., Lawton A. R., Cooper M. D. Differentiation capacity of cultured B lymphocytes from immunodeficient patients. J Clin Invest. 1973 Dec;52(12):3180–3189. doi: 10.1172/JCI107518. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES