Erythrocyte Adenosine Deaminase Activity Research Articles

Elevated erythrocyte adenosine deaminase activity in patients with acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is an often fatal disease caused by a retrovirus frequently resulting in malignancy and/or opportunistic infection. Because the immune deficiency in AIDS is similar to that in some purine enzyme deficiencies, we measured erythrocyte adenosine deaminase (ADA) and purine nucleoside phosphorylase activities in patients with AIDS, heterosexual controls, and a high-risk asymptomatic population. We found that erythrocyte ADA activity was significantly elevated in patients with AIDS (40 +/- 11 nmol/mg of hemoglobin per hr, mean +/- SD) relative to heterosexual controls (25 +/- 10, P less than 0.001). We also measured ADA activity in a group of individuals at high risk for AIDS and found that approximately half had significantly elevated ADA activities (45 +/- 4, P less than 0.002) that correlated with the presence of antibody to the lymphadenopathy retrovirus. Purine nucleoside phosphorylase activity was relatively normal in patients with AIDS as well as in individuals at risk for AIDS. Increased ADA appears to be a diagnostic marker of AIDS and may be useful in conjunction with antibody to the AIDS-related retrovirus in detecting the presence of infection in asymptomatic high-risk individuals. These data also suggest that, in addition to the lymphocyte, the erythroid cell line may also be infected by the AIDS-related retrovirus.

IMMUNOPURINOGENIC ENZYMATIC ACTIVITY IN THE ACQUIRED IMMUNODEFICIENCY SYNDROME: 132

Deficiencies of the purine catabolic enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been described in association with severe combined immunodeficiency disease and selective T-cell immunodeficiency disease respectively. Recently a selective T-cell acquired immunodeficiency syndrome has been described in homosexuals, drug addicts,Haitians and hemophiliacs. In an attempt to explore further metabolic mechanisms to account for this disorder we have quantitated erythrocyte and lymphocyte ADA and PNP activities using highly sensitive radiochemical methods in controls and seven patients with AIDS. Our results are as follows: 1) Erythrocyte ADA activity in controls and AIDS patients was 0.66 n mol/min/mg protein and 0.80 n mol/min/mg protein respectively. 2) Lymphocyte ADA activity was 6.86 n mol/min/mg protein for controls and 5.57 n mol/min/mg protein in AIDS. 3)Erythrocyte PNP activity was 2680 n mol/hr/mg protein for controls and 1618 n mol/hr/mg protein in the patients (p<.0005) 4)Lymphocyte PNP activity was 5892 n mol/hr/mg protein and 2740 n mol/hr/mg protein for controls and AIDS patients respectively (P<.0025). We conclude that: (1) Abnormalities in purine catabolic enzymes should be included in the disease spectrum of AIDS. (2) The causal relationship of decreased PNP activity in perpetuating the abnormal T-cell function in these patients remains to be determined (3) Alternatively the decreased PNP activity in AIDS may be secondary to the profound selective T-cell lymphopenia in this syndrome.

Elevated erythrocyte adenosine deaminase activity in congenital hypoplastic anemia.

Abnormalities of adenosine deaminase, a critical enzyme of the purine salvage pathway, have been reported in association with immune dysfunction, acute leukemia, and hereditary hemolytic anemia. We report data showing that erythrocyte adenosine deaminase activity is also abnormal in congenital hypoplastic anemia (the Diamond-Blackfan syndrome). Adenosine deaminase activity in erythrocytes from 12 patients (mean +/- S.D., 2.20 +/- 0.77 IU per gram of hemoglobin) was substantially greater than that observed in 50 controls (0.62 +/- 0.13 IU per gram). Enzyme activity in affected patients was also greater than that seen in cord blood or in erythrocytes from patients with hemolytic anemia, acquired aplastic anemia, Fanconi's hypoplastic anemia, acquired pure red-cell aplasia, or transient erythroblastopenia of childhood. These observations indicate that erythrocyte adenosine deaminase activity may be a unique marker for identifying congenital hypoplastic anemia.

Severe combined immunodeficiency in a child with a healthy adenosine deaminase deficient mother.

We investigated adenosine deaminase (ADA) deficient severe-combined immunodeficiency (SCID) in an 8-month-old child with ADA deficient mother. The ADA deficiency in the child was unusual in that the thymic histology was normal. In addition, the thymocytes formed E-rosettes with sheep erythrocytes and were stimulated by T-cell mitogens. ADA activity could not be detected in the child's thymocytes. Studies on the family indicated that the father had about one-half of the normal erythrocyte ADA activity. All the family members with detectable ADA activity appeared to have, according to starch gel electrophoresis of erythrocyte lysates, the common ADA-1 phenotype; however, rigorous identification of phenotype was not possible in this study. The mother had less than 1% of normal ADA activity in both erythrocyte and lymphocyte extracts, but her whole peripheral blood lymphocytes demonstrated about 6% of normal activity. Normal concentrations of ATP and small amounts of dATP were found in the mother's erythrocytes. Deoxyadenosine excretion in her urine was elevated and approximately 5-10% of that excreted by individuals with ADA deficient SCID. These studies suggest that low amounts of ADA activity in erythrocytes and blood lymphocytes of certain individuals may be compatible with good immune function and longevity.

Erythrocyte adenosine deaminase, purine nucleoside phosphorylase and phosphoribosyltransferase activity in patients with Down's syndrome

The erythrocyte adenosine deaminase, nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyltransferase and adenine phosphoribosyltransferase activities and plasma urate concentrations were measured in 20 cases of Down's syndrome and in 20 age- and sex-matched control subjects. The mean erythrocyte adenosine deaminase and adenine phosphoribosyltransferase activities and plasma urate concentrations were significantly higher in Down's syndrome subjects than in controls ( p < 0.001, p < 0.01 and p < 0.001, respectively). In all subjects studied there was a positive correlation between the erythrocyte adenosine deaminase activity and plasma urate concentration ( r = 0.488, p < 0.005). The concentrations of the erythrocyte adenine nucleotides, AMP, ADP and ATP, did not differ in Down's syndrome ( n = 10) from those of control subjects ( n = 10). The results suggest that the increase of plasma urate concentrations is a consequence of the increase in adenosine deaminase activity in Down's syndrome patients.

Physical and catalytic properties of the isozymes of adenosine deaminase from human red blood cells.

Adenosine deaminase (adenosine aminohydrolase, EC3.5.4.4) has been purified from human erythrocytes using a simple chromatographic procedure. Purified enzyme was obtained from individuals who were homozygous for the principal isozyme (ADA 1) as well as from individuals who were heterogyzous for the major variant (ADA 2-1). Although ADA 1 and ADA 2-1 are electrophoretically distinguishable, they have many common physical and catalytic properties. No significant differences between the two isozymic forms were found in measurements of molecular weight, catalytic activity in the presence of various substrates and inhibitors, pH optimum, turnover number, and stability in conditions of both high and low pH. ADA 2-1 was, however, substantially less stable than ADA 1 with respect to thermal denaturation. These studies support the idea that adenosine deaminase activity in erythrocytes is lower in those individuals who possess the variant form of the enzyme.

ELEVATED ERYTHROCYTE ADENOSINE DEAMINASE ACTIVITY IN DOWN'S SYNDROME

Erythrocyte ADA activity was measured in 29 cases of Down's syndrome and in 29 age- and sex-matched controls subjects. The mean activity (+/- S.D.) of ADA in Down's syndrome was 1883 +/- 463 mU/g Hb (37 degrees C) and 1361 +/- 294 mU/g Hb in the controls. The difference was statistically significant (p less than 0.001). The purine metabolism of Down's syndrome patients is discussed.

Adenosine deaminase activity in plasma and blood cells of patients with haematological and autoimmune diseases.

Adenosine deaminase (ADA) has been assayed in plasma, erythrocytes, and lymphocytes from 29 patients with haematological and autoimmune diseases. ADA activity was uniformly low in erythrocytes and lymphocytes from patients with non-Hodgkin lymphoma and multiple myeloma (p less than 0.001). High levels of ADA activity was found in plasma, erythrocytes, and lymphocytes from patients with myeloid leukemia (p less than 0.001). ADA was high in plasma but low in erythrocytes and lymphocytes from patients with autoimmune diseases treated with immunosuppressive drugs (p less than 0.05). 4 adults with congenital immunodeficiency showed decreased ADA activity. In the control group of normal blood donors we found a 34-year-old female with low ADA activity in plasma, erythrocytes, and lymphocytes without any immunological abnormalities. This is the 3rd case of a healthy individual deficient for ADA. 1 patient with Osler's disease and high ADA activity in erythrocytes showed the importance of the purine salvage enzyme not only in lymphocytes.

Erythrocyte adenosine-deaminase activity in gout and hyperuricemia.

Adenosine-Deaminase (adenosine-aminohydrolase EC 3.5.4.4.) (ADA) catalyses the irreversible hydrolytic deamination of adenosine to produce inosine and ammonia. Inosine is then cleaved by Purine-Nucleoside-Phosphorylase (PNP) to hypoxanthine and oxidized to xanthine and uric acid by xanthine-oxidase.

Adenosine deaminase activity in erythrocytes, lymphocytes, polymorphonuclear neutrophil leucocytes and cultured cells: A possible role in the immune response

Adenosine deaminase activity in erythrocytes, lymphocytes, polymorphonuclear neutrophil leucocytes and cultured cells: A possible role in the immune response

The activity of purine salvage pathway enzymes in murine and horse models of congenital and acquired dysimmunity

Previous studies of human congenital immunodeficiency states and in vitro observations of lymphocyte response to mitogens have implicated two purine salvage pathway enzymes, adenosine deaminase (ADA) and nucleoside phosphorylase (NP), as critical in the normal maturation and/or function of the immune system. Based on this information, ADA and NP activities were examined in a variety of congenital and acquired animal models of dysimmunity. The animals studied herein included: congenitally athymic (nude) mice; congenitally asplenic mice; congenitally athymic-asplenic mice; motheaten mice; New Zealand mice; and Arabian foals with severe combined immunodeficiency. No significant differences in the activities of ADA and NP were observed in any of these animals when compared with either normal littermates or animals with intact immune function. Major species differences were apparent when erythrocyte ADA activity was compared between mice and horses. In contrast, only minor strain alterations in ADA or NP activity were noted between several inbred groups of mice.

Absence of erythrocyte adenosine deaminase associated with severe combined immunodeficiency

Hereditary absence of adenosine deaminase activity in erythrocytes was found in an infant with severe combined immunodeficiency. Immunoglobulins were markedly decreased. Lymphocytes failed to transform with either phytohemagglutinin or concanavalin. At autopsy the thymus was rudimentary and there was a striking absence of lymphoid elements throughout the lymphoreticular system. The costochondral junction of the ribs showed widening and cupping of the metaphyseal plates, and the metaphysis of the long bones demonstrated lucent bands suggestive of a defect in ossification. The association of combined immunodeficiency with the genetically determined absence of erythrocyte-type adenosine deaminase appears now to be a specific clinical entity.

Adenosine deaminase deficiency in a child with severe combined immunodeficiency

A case is reported of an apparent total erythrocyte adenosine deaminase (ADA) deficiency in a girl suffering from severe combined immunodeficiency (c.i.d.). Four other erythrocyte enzymes investigated showed apparent normal activity. The ADA activity in erythrocytes from her parents was about half normal, suggesting that the girl had inherited a chromosome pair without information for normal red cell ADA‐isoenzymes. The suspected chromosome deficit may have affected the ADA locus only, or it may involve a more extensive part of a chromosome including the ADA locus. In another child, a boy exhibiting clinically the same immunodeficiency syndrome, the ADA type and ADA activity were found to be normal. Recently, two other cases of lack of red cell ADA activity, both affecting girls with similar manifestations of immunological deficiency, have been reported from the U.S.A. (Giblett et al. 1972). These findings indicate that coexistence of a total lack of red cell ADA activity and some immunodeficiency syndromes may be a common condition.