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):1179-83. doi: 10.1016/s0140-6736(75)92661-6.

Abstract

Three patients with the Lesch-Nyhan syndrome were found to have normal delayed hypersensitivity, peripheral-blood T-lymphocyte counts, lymphocyte responses to P.H.A., and serum IgM, IgA, and IgE levels. However, the percentages of B-lymphocytes, IgG levels, serum-isohaemagglutinin titres, and lymphocyte responses to pokeweed mitogen (P.W.M.) were subnormal. These observations suggest that activity of the salvage pathway of purine synthesis catalysed by hypoxanthine-guanine phosphoribosyl transferase (H.G.P.R.T.) is not required for the responses of T-lymphocytes to mitogenic or antigenic stimulation, but may contribute to the proliferation and function of B lymphocytes. The major role of the de-novo pathway of purine synthesis in human lymphocyte responses to mitogenic or antigenic stimulation is shown by the effects of inhibitors of this pathway, including immunosuppressive agents, and by the effects of congenital deficiency or inhibition of adenosine deaminase.

Publication types

  • Case Reports

MeSH terms

  • Adenosine Deaminase / deficiency
  • Adolescent
  • Azaserine / pharmacology
  • B-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Hemagglutinins / isolation & purification
  • Humans
  • Hypersensitivity, Delayed / diagnosis
  • Hypoxanthine Phosphoribosyltransferase / deficiency
  • Immunoglobulins / isolation & purification
  • Immunologic Deficiency Syndromes / complications*
  • In Vitro Techniques
  • Lectins / pharmacology
  • Lesch-Nyhan Syndrome / etiology
  • Lesch-Nyhan Syndrome / immunology*
  • Lymphocyte Activation*
  • Lymphocytes / drug effects
  • Male
  • Mercaptopurine / pharmacology
  • Mitogens / immunology
  • Purines / biosynthesis*
  • T-Lymphocytes / immunology
  • Thymidine / antagonists & inhibitors

Substances

  • Hemagglutinins
  • Immunoglobulins
  • Lectins
  • Mitogens
  • Purines
  • Azaserine
  • Mercaptopurine
  • Hypoxanthine Phosphoribosyltransferase
  • Adenosine Deaminase
  • Thymidine