Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vivo murine model for immunodeficiency of both B and T cells is produced by continuous intraperitoneal infusion of 2'-deoxycoformycin (DCF), a specific tightly binding inhibitor of adenosine deaminase (ADase; adenosine aminohydrolase, EC 3.5.4.4). After DCF infusion, ADase of thymus, spleen, and lymph nodes was inhibited to varying degrees ranging from 57% to 100%. Immunodeficiency under these conditions was indicated by: (i) a striking decrease in lymphocyte response to the T-cell mitogens concanavalin A and phytohemagglutinin; (ii) an impairment of delayed hypersensitivity measured by the footpad reaction; (iii) a decrease in antibody production measured in both in vivo and in vitro plaque-forming cell assay; (iv) a significant prolongation of mouse skin allograft survival after transplantation into the C57BL/6J (H-2b) strain of skin from BALB/c (H-2d) mice; and (v) a marked lymphopenia. Histological examination indicated lymphoid degeneration in the thymus, lymph nodes, and spleen with no alterations in other tissues including bone marrow, kidney, lung, gastrointestinal tract, and liver except for the occurrence of hepatitis. A decrease in the number of Thy-1-positive cells in both spleen and lymph nodes further supported the fact of cytotoxicity of DCF to T cells. Anorexia and weight loss were observed within 5 days of continuous DCF infusion at 0.4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man.
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PMID:Animal model for immune dysfunction associated with adenosine deaminase deficiency. 696 8

Purine nucleoside phosphorylase (PNP) deficiency is an immunodeficiency disorder characterized by recurrent infections, failure to thrive and neurologic symptomatology. While enzyme replacement therapy (ERT) is a therapeutic option for adenine deaminase (ADA) deficiency, a similar disorder, this is not available for PNP deficiency, and bone marrow transplant (BMT) is the only treatment option. Moreover, even with BMT, improvement of neurological deficits is not definite. We describe a 16-month-old boy who underwent BMT for PNP deficiency which resulted not only in freedom from infections but also in neurological improvement and autologous T-cell recovery.Pre-transplant, this child had severe lymphopenia with recurrent infections and psychomotor retardation. Post-transplant, in the presence of mixed chimerism, he had normal lymphocyte count, including presence of recipient T cells and neurological improvement. The re-emergence of recipient T cells, when there were virtually no such cells pre-transplant, and the neurological improvement are indicative of improvement of the enzyme deficiency in tissues which remain genetically enzyme depleted.These defects are not directly corrected by BMT, but are due to delivery of the missing enzyme by the transplanted tissue. In this aspect, transplantation in PNP deficiency is similar to transplantation in other inborn errors of metabolism where the engrafted donor cells deliver enzyme and restore function to deficient tissues. This further lends support to the recommendations that BMT should be the favoured treatment option in disorders like ADA deficiency or Hurler syndrome, where, even though ERT is available, it is limited by inability to correct the central nervous system defects.
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PMID:Cross correction following haemopoietic stem cell transplant for purine nucleoside phosphorylase deficiency: engrafted donor-derived white blood cells provide enzyme to residual enzyme-deficient recipient cells. 2343 Sep 37