High adenosine deaminase activity in the pleural effusion of a patient with Legionnaires' disease

Abstract:   Although Legionnaires' disease (LD) is frequently accompanied by pleural effusion, the characteristics of pleural effusions in LD have not been well studied. Levels of adenosine deaminase (ADA) activity in pleural fluid >40 IU/L have a high sensitivity (81–100%) and specificity (83–100%) for tuberculosis. ADA activity in pleural effusions due to LD has not been previously reported. The case of a patient with LD complicated by a pleural effusion with high ADA activity is reported. In countries where the prevalence of tuberculosis is high and pleural fluid ADA activities are frequently measured, LD should be included in the differential diagnosis of an exudative pleural effusion with high ADA activity.     

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.     

A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan

A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38-year-old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; ⁵¹ Cr-labeled red cell half-life, 12 days; red cells showed moderate stomatocytosis. His red cell ADA activity showed 40-fold increase while that of the mother showed 4-fold increase. The mother was hematologically normal. The father had a normal enzyme activity. The proband and the mother showed slightly high serum uric acid levels. The proband's red cell showed: ATP, 628 nmoles/ml (normal, 1,010-1,550); adenine nucleotide pool, 46% of the normal mean; 2,3-diphosphoglycerate content, 3,782 nmoles/ml (normal 4,170-5,300); increased oxygen affinity of hemoglobin, P₅₀ of intact crythrocytes being 21.8 mmHg (normal, 24.1-26.1). Red cell glycolytic intermediates in the proband were low in general, and the rate of lactate production was low. Kinetic studies using crude hemolysate revealed a normal Km for adenosine, normal electrophoretic mobility but slightly abnormal pH curve and slightly low utilization of 2-deoxyadenosine. The ADA activity of lymphocytes was nearly normal.     

A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency

Adenosine deaminase (ADA) deficiency is an inherited disorder which leads to elevated cellular levels of deoxyadenosine triphosphate (dATP) and systemic accumulation of its precursor, 2-deoxyadenosine. These metabolites impair lymphocyte function, and inactivate S-adenosylhomocysteine hydrolase (SAHH) respectively, leading to severe immunodeficiency. Enzyme replacement therapy with polyethylene glycol-conjugated ADA is available, but its efficacy is reduced by anti-ADA neutralising antibody formation. We report here carrier erythrocyte encapsulated native ADA therapy in an adult-type ADA deficient patient. Encapsulated enzyme is protected from antigenic responses and therapeutic activities are sustained. ADA-loaded autologous carrier erythrocytes were prepared using a hypo-osmotic dialysis procedure. Over a 9-yr period 225 treatment cycles were administered at 2-3 weekly intervals. Therapeutic efficacy was determined by monitoring immunological and metabolic parameters. After 9 yr of therapy, erythrocyte dATP concentration ranged between 24 and 44 micromol/L (diagnosis, 234) and SAHH activity between 1.69 and 2.29 nmol/h/mg haemoglobin (diagnosis, 0.34). Erythrocyte ADA activities were above the reference range of 40-100 nmol/h/mg haemoglobin (0 at diagnosis). Initial increases in absolute lymphocyte counts were not sustained; however, despite subnormal circulating CD20(+) cell numbers, serum immunoglobulin levels were normal. The patient tolerated the treatment well. The frequency of respiratory problems was reduced and the decline in the forced expiratory volume in 1 s and vital capacity reduced compared with the 4 yr preceding carrier erythrocyte therapy. Carrier erythrocyte-ADA therapy in an adult patient with ADA deficiency was shown to be metabolically and clinically effective.     

高血压病患者淋巴细胞内腺苷脱氨酶与白细胞介素Ⅱ相关性的研究

采用分光光度法及双抗夹心法对24例高血压病（EH）患者的淋巴细胞内腺苷脱氨酶（LADA）活性及白细胞介素Ⅱ（IL－2）水平进行检测。并与20例正常人对照，结果表明：EH患者LADA活性、IL－2水平均低于正常人（均P＜0．01）；EH患者IL－2与血压呈负相关（r＝－0．825P＜0．05）；EH患者LADA活性与IL－2呈正相关（r＝7．991P＜0．05）。提示EH患者存在IL－2改变，IL－2与血压的形成有内在联系。说明EH患者存在免疫改变，免疫参与了EH患者病理过程，EH患者LADA活性降低可能是导致IL－2水平下降的基本原因之一。     

Determination of adenosine deaminase activity and its isoenzymes for diagnosis of pleural effusions

OBJECTIVE: We aimed to investigate adenosine deaminase (ADA) activity and the activities of its ADA1 and ADA2 isoenzymes in pleural effusions and also sera with different aetiological origins. METHODOLOGY: The pleural effusions of 87 patients were examined. The patients were separated into four groups: transudates, parapneumonic, malignant, and tuberculous effusions. The cases were also designated as tuberculous or non-tuberculous group. Adenosine deaminase activity was determined by the colorimetric method described by Giusti and Galanti. RESULTS: The intermean differences were statistically significant for total ADA, ADA1 and ADA2, except for pleural fluid ADA1 in the malignant group when compared to the tuberculous effusion group. The intermean differences between the tuberculous and non-tuberculous group were statistically significant for all three parameters except for pleural fluid and serum ADA1 activity. The sensitivities of total ADA, ADA1 and ADA2 activities for tuberculosis were 91, 57 and 93%, respectively; their specificities 89, 88 and 92%, respectively; their positive predictive values 82, 70 and 86%; and their diagnostic accuracies 89, 76 and 92%, respectively, in pleural fluid. CONCLUSIONS: Determination of ADA and its isoenzymes can help to differentiate the causes of pleural effusion. Increased ADA2 activity is a striking marker of tuberculous effusions. In contrast, increased ADA1 activity was significantly elevated in parapneumonic effusions.     

腺苷脱氨酶诊断结核性脑膜炎价值Meta分析

目的通过Meta分析确定检测脑脊液(CSF)中腺苷脱氨酶(ADA)的含量是否有助于结核性脑膜炎的早期诊断。方法检索Medline,Embase,BIOSIS和Cochrane等数据库,检索时间为1995年1月至2009年12月,收集关于测定CSF中ADA以诊断结核性脑膜炎的相关英文文献,并用QUADAS标准进行质量评价,采用Metadisc1.4和SPSS13.0软件,用随机效应模型汇总各研究中ADA诊断结核性脑膜炎的敏感度、特异度以及其他指标,绘制汇总受试者工作特征曲线并探讨其诊断特性。结果最终有9项独立研究纳入本次Meta分析,ADA诊断结核性脑膜炎的总体敏感度0.77(95%CI 0.72～0.82);特异度0.91(95%CI 0.90～0.93);阳性似然比7.93(95%CI 5.85～10.76),阴性似然比0.28(95%CI 0.19～0.41),合并受试者工作特征曲线下面积为0.9129,但在结核性脑膜炎与化脓性脑膜炎的鉴别诊断中特异度降为0.75(95%CI 0.67～0.82)。结论 ADA诊断结核性脑膜炎的敏感度、特异度均较高,检测CSF中的ADA有助于结核性脑膜炎的诊断,但在与化脓性脑膜炎相鉴别时诊断效力下降,需参考其他检测指标。     

Comparative activity of erythrocyte adenosine deaminase and orotidine decarboxylase in Diamond-Blackfan anemia

It previously has been reported that red blood cells (RBC) of patients with Diamond-Blackfan syndrome (DBS) have increased activity of orotidine decarboxylase (ODC) and adenosine deaminase (ADA). The studies reported here compared the activity of these two enzymes in DBS erythrocytes, cord blood, and reticulocytes. The activity of ODC, although increased in some DBS erythrocytes, was not significantly different from that seen in cord RBC or reticulocytes. In contrast, RBC-ADA activity was increased in 23 of 26 DBS patients; and this enzyme elevation was distinct from that seen in cord blood and reticulocytes. Moreover, ADA activity was normal in 26 of 27 patients with transient erythroblastopenia of childhood (TEC). Taken together, these data indicate RBC-ADA activity is more sensitive than ODC as a marker of DBS. In addition, RBC-ADA activity continues to be useful for distinguishing DBS and TEC in most patients with RBC hypoplasia.     

Plasma adenosine deaminase2 is a marker for human immunodeficiency virus-1 seroconversion.

Plasma adenosine deaminase2 (ADA2) has recently been proposed to be a marker for human immunodeficiency virus-1 (HIV) infection. We measured ADA2 levels in plasma from two groups of white homosexual males at 6-month intervals for a total of 2.5 years. One group consisted of 6 subjects who seroconverted for HIV, and the other consisted of 8 HIV seropositive patients who progressed from asymptomatic (CDC Groups II/III) to symptomatic (CDC Group IV) disease. Seroconversion was associated with a significant increase in plasma ADA2 which persisted throughout follow-up of 1.5 years. However, disease progression in HIV seropositive patients was not associated with any significant change in plasma ADA2. In conclusion, ADA2 may represent a unique marker for HIV seroconversion which does not change with later progression to symptomatic disease.     

Effect of adenosine deaminase inhibition with pentostatin on myocardial stunning in dogs

Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine deaminase and has been demonstrated to augment endogenous adenosine levels during regional and global myocardial ischemia. Based on the rationale that increasing endogenous adenosine during ischemia may be cardioprotective, the objective of this study was to determine if adenosine deaminase inhibition with pentostatin could improve postischemic contractile dysfunction (stunning) in open-chest anesthetized dogs. All animals underwent 15 min of coronary occlusion followed by 3 h of reperfusion preceded by an intravenous bolus of either 0.2 mg/kg of pentostatin (n=8) or saline (n=7). Sonomicrometers were plced in the ischemic area and were used to measure systolic wall thickening before, during, and after occlusion of the left anterior descending artery. Myocardial blood flow was measured with tracer labeled microspheres at baseline, 10 min of occlusion and at 1 h of reperfusion. Both groups were equally dyskinetic during occlusion (–21±5% of baseline thickening in the controls and –28±8% in the pentostatin group). The pentostatin group, however, demonstrated better contractile function at all time points during reperfusion, which was significantly different from the control group at 3 h of reperfusion. The improvement in regional function in the pentostatin group was not due to significant disparities in hemodynamic variables, size of the region at risk, or in collateral blood flow. These results indicate that pentostatin can ameliorate the severity of myocardial stunning, an effect we propose is due to increasing endogenous levels of adenosine during the ischemic interval. Although significant improvement was detected with pentostatin, the improvement was modest compared to controls, suggesting that the utility of inhibiting adenosine deaminase to modify regional mechanical stunning is limited.Presented in part at the 1993 American Heart Association Scientific Sessions in Atlanta, GA     

Characterization of adenosine deaminase (ADA)-negative B-lymphoblastoid cells cocultured with ADA-positive fibroblasts

Abstract: A cell line, BAD05, derived from B lymphocytes of an adenosine deaminase (ADA; EC 3,5,4,4)-deficient patient could not proliferate in a serum-free medium containing 100 μmol/l deoxyadenosine. When BAD05 was cultured with ADA-positive fibroblasts, the proliferation of BAD05 was improved. BAD05 cell density increased when the initially mixed ratio of fibroblasts/BAD05 was 1/10 or higher, but decreased when the ratio was 1/20 or lower. Deoxyadenosine concentrations in the medium and ATP and deoxyATP (dATP) levels in the BAD05 were measured after 4 hours of coculture at initial BAD05 cell densities of 1 × 10⁵and 1 × 10⁶cells/ml. Deoxyadenosine concentrations in the medium decreased as the density of fibroblasts increased. The dATP level decreased as the mixed ratio rose. The ratio of fibroblasts/BAD05 rather than the cell density of fibroblasts had a larger effect on the dATP levels in BAD05. Under our experimental conditions, ADA-negative cells proliferated well when the ratio of ADA-positive cells/ADA-negative cells was over 1/10.     

腺苷脱氨酶活性与肝脏疾病的关系

目的：探讨腺苷脱氨酶在肝脏疾病中的诊断价值。方法：应用全自动生化分析仪检测肝病患者血清腺苷脱氨酶（ADA）及肝功能各项指标。结果：脂肪肝患者血清ADA无明显升高；慢性乙型肝炎、急性肝炎、肝硬化及肝硬化合并肝癌患者血清ADA活性明显增高，与正常组比较有统计学意义（P〈0．01）；肝硬化患者、肝硬化合并肝癌患者血清ADA活性较慢性乙型肝炎患者明显升高，两组比较有统计学意义P〈0．01）；急性肝炎患者经治疗血清ADA明显降低，与发病早期比较有统计学意义（P〈0．05）；肝病患者血清ADA与白球蛋白比值、前白蛋白呈负相关，与总胆红素呈正相关。结论：肝病患者血清ADA增高提示肝病慢性化、逐渐进展，反映肝脏损害程度加重，肝脏储备、合成功能逐渐降低。     

Frequency of low erythrocyte porphobilinogen deaminase activity in Finland.

The frequency of low erythrocyte porphobilinogen deaminase (PBGD) activity was investigated in 2234 blood donors and in 30 patients with acute intermittent porphyria. The mean enzyme activities (+/- SD) were 3.38 +/- 0.58 U and 1.82 +/- 0.41 U, respectively. Eighteen blood donors without any history of symptoms of porphyria or haematological disease had low PBGD activity (less than 2.20 U), and they were studied further. All of them also had subnormal concentrations of the erythrocyte enzyme protein, as determined by an immunological method. Lymphocyte PBGD activity was within the normal range, but this parameter does exhibit a wide overlap between normal and porphyric values. Urinary excretion of porphobilinogen was moderately increased in two of the blood donors. In four of the 18 families of the blood donors with low PBGD activity several first-degree relatives had low erythrocyte enzyme activity, consistent with a dominant mode of inheritance. The 5-aminolaevulinic acid loading-test was normal in the blood donors with familial occurrence of low erythrocyte PBGD. It is concluded that inherited defects in erythrocyte PBGD occurred among Finnish blood donors with a frequency of about 1 in 500. The defects may be identical with those in acute intermittent porphyria (AIP), but other mechanisms are also possible, e.g. a mutation in the erythroid-specific part of the PBGD gene.     

Influence of storage time and temperature on pleural fluid adenosine deaminase determination

OBJECTIVES AND BACKGROUND: The determination of adenosine deaminase (ADA) activity in pleural fluid is important for differentiation of pleural effusions and diagnosing pleural tuberculosis. Although measurement of ADA is simple and inexpensive, controversies exist regarding potential errors caused by time elapsed between sample collection and analysis, storage temperature and the use of anticoagulants. The objective of this study was to evaluate the influence of storage time (1, 3, 7, 10 and 28 days) and temperature (4 degrees C and -20 degrees C) on the determination of ADA in pleural fluid samples collected in EDTA and sent at ambient temperature to the laboratory for initial processing within 1 h of collection. METHODOLOGY: Twenty-seven pleural exudates obtained from 20 patients with neoplastic disease and seven with tuberculosis were analysed. The ADA activity obtained within 1 h of collection was considered the gold standard and was compared with the other measurements. RESULTS: The correlation between the initial measurement and all others was >or=0.90 for both temperatures up to the 10th day after thoracocentesis and tended to decrease by 28 days after collection, but this difference was not significant. CONCLUSIONS: Pleural fluid samples collected in EDTA and sent for analysis within 1 h after collection can be used to determine ADA up to 28 days after collection if stored at 4 degrees C or -20 degrees C, with no evidence of significant increases or decrease in enzyme activity that might distort the results.     

血清腺苷脱氨酶对慢性HBV感染者显著肝纤维化的诊断价值

目的探讨血清腺苷脱氨酶(ADA)诊断慢性HBV感染者显著肝纤维化的价值。方法选取2011年5月-2016年10月在宁波市第二医院接受肝活组织检查的493例慢性HBV感染者,根据肝纤维化程度将所有患者分为S0~S4级,S0级79例,S1级254例,S2级103例,S3级35例,S4级22例。常规检测TBil、ALT、AST、ALP、GGT、Alb、ADA等生化指标和血常规指标,计算AST/PLT比值指数(APRI)。比较不同分级患者各指标的差异。正态分布的计量资料多组间比较采用方差分析,偏态分布计量资料组间比较采用Kruskal-Wallis H检验。计数资料组间比较采用χ~2检验。对各指标进行二分类logistic回归,采用受试者工作特征曲线(ROC曲线)分析ADA、APRI单独及多指标联合应用对显著肝纤维化(S≥2)的诊断价值。结果年龄、性别、TBil、ALT、AST、ALP、GGT、Alb、ADA和APRI在S0~S4级肝纤维化患者中比较,差异均有统计学意义(F=11.41,χ~2值分别为14.45、15.08、28.27、48.22、48.65、80.53、17.03、57.89、73.20,P值均<0.05)。性别、年龄和血清ADA是显著肝纤维化的独立危险因素(比值比分别为2.59、1.05、1.12,P值均<0.01)。ADA、APRI及多指标联合应用诊断显著肝纤维化均有一定价值(P值均<0.01),ROC曲线下面积分别为0.70、0.73和0.75。结论血清ADA对慢性HBV感染者显著肝纤维化有一定的辅助诊断价值。     

胸腔积液腺苷脱氨酶对内科胸腔镜检查临床病例选择的意义

目的 探讨胸腔积液腺苷脱氨酶(ADA)对内科胸腔镜检查临床病例选择的意义.方法 回顾性分析2013年1月至2016年4月经内科胸腔镜检查的不明原因胸腔积液患者198例,分为青年组、中年组和老年组,以胸腔积液ADA≥45 U/L或ADA≥45 U/L联合淋巴细胞占白细胞比例≥50％作为诊断结核性胸膜炎的标准,确定其敏感度和特异度,并分析性别、年龄对ADA的影响.结果 内科胸腔镜对不明原因胸腔积液的诊断率为98.9％.胸腔积液ADA≥45 U/L诊断结核性胸膜炎的敏感度68.7％,特异度88.1％;胸腔积液ADA≥45 U/L联合淋巴细胞占白细胞比例≥50％诊断结核性胸膜炎的敏感度70.2％,特异度96.3％,尤其是在青年组,其诊断特异度达100％.结论 对于不明原因胸腔积液的青年患者,如果胸腔积液ADA≥45 U/L且淋巴细胞占白细胞比例≥50％,可考虑诊断性抗结核治疗;对中老年不明原因胸腔积液,建议常规行内科胸腔镜检查,避免误诊.