Elevated adenosine deaminase and purine nucleoside phosphorylase activity in peripheral blood null lymphocytes from patients with acquired immune deficiency syndrome

Abstract

The purine metabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) are important in lymphocyte differentiation, and genetic deficiencies of either enzyme have been associated with hereditary immunodeficiency states. Both ADA and PNP activity were measured in null cell-enriched and T cell-enriched peripheral blood lymphocytes from 16 patients with the acquired immune deficiency syndrome (AIDS), seven patients with the AIDS-related symptom complex (ARC), and seven asymptomatic homosexuals. ADA activity in nmol/10(6) lymphocytes/h was significantly elevated in null lymphocytes from AIDS (161 +/- 12) as compared with 23 healthy heterosexual controls (127 +/- 8;P less than .025). PNP activity was also significantly increased in null lymphocytes from AIDS patients (96 +/- 10;P less than .005) as well as those from ARC patients (84 +/- 11:P less than .025) relative to controls (61 +/- 5). No significant differences in enzyme activity were noted in T cell-enriched cells in any group. Along with elevated enzyme activity, AIDS patients had small yet significant increases in the percentages of HLA-DR (P less than .025), terminal deoxynucleotidyl transferase (TdT) (P less than .0001), and peanut agglutinin receptor (P less than .0001) positive lymphocytes in the null fraction compared with controls. TdT-positive cells appeared morphologically as large lymphoblasts with irregular nuclei. The data imply that the cellular immune deficiency in AIDS is not a result of deficiencies in lymphocyte ADA or PNP activity, but is more likely associated with an increase in an immature and/or activated lymphocyte subset.

Immunological dysfunction in HIV‐1‐infected individuals caused by impairment of adenosine deaminase‐induced costimulation of T‐cell activation

“…Indeed, the inhibition of ADA binding to CD26 by viral particles is likely to occur in vivo , as it has been shown that the 50% inhibitory concentration (IC 50 ) for inhibition of ADA binding to the Jurkat T‐cell line is similar to the dissociation constant ( K d or affinity) values reported for binding of gp120 to CD4 43,67 . However, ADA is found at high levels in the serum of HIV‐infected patients, 68–73 and this could be, at least in part, attributable to the displacement of ADA from its anchor on the T‐cell surface. As previously reported, a CD4–gp120 interaction is required for efficient inhibition of ADA binding to CD26 44 …”

Spontaneous Apoptosis, Oxidative Status and Immunophenotype Markers in Blood Lymphocytes of AIDS Patients

“…Functional, morphologic and structural differences in mononuclear cells, including the T/B/NK subsets and monocytes, in healthy subjects and HIV+/AIDS patients have been consistently reported for some time [23,25,27]. But the cytoplasmic metabolic processes [1] in immunocompetent PBM cells have received less detailed investigation, apart from the purine and pyrimidine enzymatic and metabolic pathways [33,34,44], and most of these studies have concerned the cell surface, mitochondria and nuclear organelles [13,24,32,38]. The antioxidant status and redox related pathways have recently received increased attention, since it has been suggested that oxidative stress could be implicated in several aspects of the pathogenesis of HIV disease, including viral replication, inflammatory response, decreased immune cell proliferation, loss of immune function and apoptotic cell death [35].…”

An old enzyme for current needs: adenosine deaminase and a dendritic cell vaccine for HIV

“…[29][30][31] Moreover, ADA binding to CD26 is inhibited by HIV-1 envelope glycoprotein gp120, resulting in impaired ADA co-stimulation in cells of HIV-infected individuals. 32,33 Although it remains unclear whether high levels of ADA accumulate in the serum of HIV-infected patients when gp120 disrupts the interaction between ADA-CD26, [34][35][36][37][38] gp120 can reduce both the ADA-induced secretion of cytokines and ADA-enhanced T-cell proliferation in HIV-infected individuals. 32 Importantly, the effect of ADA in cells from HIV-infected patients is positively correlated with the percentage of CD4 + cells and nadir CD4 counts, and it is negatively correlated with viral load.…”