High Adenosine Deaminase Activity Research Articles

Vitamin D Reduces the Activity of Adenosine Deaminase and Oxidative Stress in Patients with Type Two Diabetes Mellitus.

Patients with Type 2 diabetes mellitus (T2DM) have lower levels of vitamin D. An elevation in uric acid (UA) contributes to T2DM via an increase in oxidative stress. Adenosine deaminase (ADA) is an enzyme of the purine degradation pathway. It is hypothesized that a reduction of ADA activity via vitamin D supplementation reduces UA and oxidative stress. A total of 162 participants (81 with T2DM and 81 controls) are enrolled in a case-control study. A follow-up interventional study is performed on 30 patients with vitamin D deficiency. These patients receive 50000 IU (international units) of vitamin D3 on a weekly basis for 12 weeks. This intervention is followed by the measurement of several markers. T2DM patients has higher ADA activity, UA, and lipid peroxidation but lower 25-hydroxy-vitamin D (25 (OH) vitamin D) and GSH/GSSG ratio (p<0.05). Vitamin D supplementation results in a reduction of ADA activity and UA levels (p<0.05) along with an increase in GSH/GSSG ratio (p<0.05). The results highlight the presence of an axis in T2DM patients between ADA, UA, and oxidative stress. Modulation of this axis can be achieved by clinically approved vitamin D supplementation protocols.

Adenosine deaminase and cytokines associated with infectious diseases as risk factors for inflammatory arthritis and methotrexate as a potential prophylactic agent

Rheumatoid arthritis (RA), is an autoimmune disease resulting in inflamed joints with erosions and deformities. A complex interaction of genetic factors concomitant with a specific immune response against a variety of environmental factors might play a pivotal role in determining susceptibility to RA. RA is known to have infections as trigger points to develop autoimmunity and antibodies prior to the presentation of symptoms clinically. Infections beckon both the innate and the adaptive immune systems. The inflammatory cells such as macrophages and lymphocytes secrete Adenosine deaminase (ADA), an important enzyme in purine metabolism, which through deamination converts the extracellular adenosine to inosine causing a dip in adenosine levels and shifting the immune balance towards pro-inflammatory response. ADA induces production of inflammatory cytokines such as tumor necrosis factor alpha (TNFα), transforming growth factor beta (TGFβ), and interferon gamma (IFNγ). Infections parse as well as ADA activity can also lead to citrullination (deamination) which enhances auto-antibody production and can lead to systemic inflammation prior to the clinical symptoms of RA. So, the conversion of arginine to citrulline by peptidyl arginine deiminase enzyme (PAD) may be an important precursor to the development of RA. These antibody titers are maintained by ADA even after post infection by keeping the pro-inflammatory bias making it a chronic condition in RA. This eventually leads to joint erosions by enhanced osteoclastic activity, cartilage degradation, synoviocyte proliferation and reduced differentiation of osteoblasts from mesenchymal stem cells and also their mineralization. Methotrexate, a disease-modifying antirheumatic drug (DMARD) used for RA treatment can be used as a prophylactic agent to prevent the patients of high ADA activity, elevated cytokines and high anti-CCP antibodies titers from developing RA.

Abstract PO-152: Metabolic rewiring in African-American prostate cancer: A role for adenosine-inosine axis

Abstract African-American (AA) men have a 60% higher incidence of prostate cancer compared to European-American (EA) men and tend to have a more aggressive clinical outcome. An understanding of the altered biological responses and the factors that lead to health disparity in prostate cancer development and progression is unclear. Metabolism defines the physiological state of the cell and metabolic reprogramming is a hallmark of cancer. Thus, studying the metabolic landscape will be critical for understanding the biological changes that might contribute to this disparity. Analysis of 190 metabolites across prostate cancer/benign adjacent tissue pairs from ancestry typed AA and EA men performed in our laboratory, revealed altered levels of adenosine and inosine. High inosine to adenosine ratio is observed in AA men compared to EA men. In line with this finding, the enzyme adenosine deaminase (ADA), which converts adenosine to inosine was found elevated in AA men, potentially explaining the high inosine to adenosine ratio in AA PCa. The effects of these metabolic alterations on AA PCa progression are unknown. The current study will address the knowledge gap on the consequences of elevated ADA activity in AA PCa and attempt to dissect its role in effecting an aggressive phenotype in PCa. To determine the role of elevated ADA in PCa, it was overexpressed in ancestry-typed AA (MDA-PCa-2A) and EA PCa(LNCaP) cell lines (termed ADA OE). Phenotypic examination of these cells revealed increased ADA enzyme activity decreases the cell-ECM adhesion. Molecular analyses revealed a significant reduction in Tenascin C(TNC), a matrix protein known for its anti-adhesive properties. TNC is critical for modulating cell motility and adhesion. TNC is also a marker for the reactive stromal microenvironment. Therefore, we evaluated the effects of altered adenosine-inosine levels on stromal cells. TNC induction was observed in stromal cells upon treatment with ADA OE conditioned media and inosine addition. These molecular findings suggest that high ADA activity could facilitate adhesion decrease and modulate the stromal microenvironment to aid in the metastatic dissemination from the primary tumor. From a translational viewpoint, ADA enzyme activity could serve as a biomarker for metastatic prostate cancer. Therefore, we further look to analyze the inosine to adenosine levels in patient samples and correlate with various clinical outcomes in PCa. Our initial analysis reveals high inosine to adenosine ratio in biopsy positive patient samples compared to biopsy negative samples. Our next steps of analysis include correlating the enzyme activity with (i)Biochemical Recurrence(BCr) (ii)Time to attaining castration resistance in castration-sensitive patients (iii)Time to metastasis (iv)Response to Androgen deprivation in patients after BCr. Based on our current findings, we expect the inosine to adenosine ratio in plasma or urine to serve as a predictive marker for PCa incidence or progression in AA men. In addition, we expect ADA to serve as a potential therapeutic target for AA PCa. Citation Format: Christy Charles. Metabolic rewiring in African-American prostate cancer: A role for adenosine-inosine axis [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-152.

The negative impact of increasing age and underlying cirrhosis on the sensitivity of adenosine deaminase in the diagnosis of tuberculous peritonitis: a cross-sectional study in eastern China

BackgroundOur study aimed to evaluate the correlation between the sensitivity of adenosine deaminase (ADA) testing for the diagnosis of tuberculous peritonitis (TBP) and patient age or cirrhosis status. MethodsClinical data for patients clinically diagnosed with TPB (n = 132) or not (n = 147) were assessed. ADA activity was compared among three age groups (< 45 yr, 45–60 yr, and ≥ 60 yr) and among cirrhosis-related subgroups. Cut-off values for the ADA test were analyzed among three patient populations (young non-cirrhotic, n = 97; older non-cirrhotic, n = 115; cirrhotic, n = 67), and validated in a cohort of 259 participants. ResultsAccording to the multivariate regression analyses, age < 45 yr is highly predictive of TBP risk. The young non-cirrhotic TBP patients had higher ADA activity than the middle-aged or old controls (p < 0.01). Significantly decreased activity and efficacy of ADA were observed in the cirrhotic subgroup/population, regardless of age or cohort. For the above-mentioned two non-cirrhotic populations in the validation cohort, the ADA test showed excellent performance using thresholds of 30.5 IU/L and 20.5 IU/L, with respective sensitivities of 91.1% and 92.6%. ConclusionsADA activity is negatively associated with increasing age and underlying cirrhosis. Optimizing cut-off values for the ADA test can increase its sensitivity in non-cirrhotic individuals older than 45 years.

THE IMPORTANCE OF URATE PATHWAY ENZYMES ACTIVITY AND ITS RELATION WITH OXIDATIVE STRESS IN PROGRESSION AND INVASION OF HUMAN COLORECTAL CANCER

Colorectal cancer (CRC) is one of the main reasons for the mortality connected with tumor diseases. There is still a shortage of examination including the influence of urate pathway enzymes in the progressiveness and invasion of CRC, so the present study investigated the role of xanthine oxidase (XO), adenosine deaminase (ADA) and 5'-nucleotidase (5'-NT) activity, concerning TBA-reactive substances (TBARS) as an oxidative stress (OS) marker in progression, also an invasion of human colorectal cancer. We took tissue specimens from 50 patients with colon cancer, in all four TNM clinical stages of the disease. They were divided into 3 groups: cancer tissue, tissue surrounding the tumor and healthy control tissue group. We made 10% homogenates in which we conducted the study with proper methods. The activity of ADA and XO in tumor tissue and tissue adjacent to the tumor is statistically higher in comparison to healthy colon tissue. The 5'-NT is not significantly higher in carcinoma tissue. The highest activity of ADA and XO is in T2 and T3 tumor stages. TBARS has the highest concentration in T3 and T4 stages of the tumor. Presented results suggest that the possible cause of OS in colon carcinoma is high XO and ADA activity. It may include those enzymes in the transformation of the colon tissue, as well as in the progression of CRC. So, the ADA and XO activity might be helpful in determing the margins of colon resection. They can have significance in diagnosis, but in the prognosis of the disease as well.

Mutations in Ribosomal Protein S19 Gene and Diamond Blackfan Anemia: Wide Variations in Phenotypic Expression

AbstractMutations of the ribosomal protein S19 (RPS19) gene were recently identified in 10 patients with Diamond Blackfan anemia (DBA). To determine the prevalence of mutations in this gene in DBA and to begin to define the molecular basis for the observed variable clinical phenotype of this disorder, the genomic sequence of the 6 exons and the 5′ untranslated region of the RPS19 gene was directly assessed in DBA index cases from 172 new families. Mutations affecting the coding sequence of RPS19 or splice sites were found in 34 cases (19.7%), whereas mutations in noncoding regions were found in 8 patients (4.6%). Mutations included nonsense, missense, splice sites, and frameshift mutations. A hot spot for missense mutations was identified between codons 52 and 62 of the RPS19 gene in a new sequence consensus motif W-[YFW]-[YF]-x-R-[AT]-A-[SA]-x-[AL]-R-[HRK]-[ILV]-Y. No correlation between the nature of mutations and the different patterns of clinical expression, including age at presentation, presence of malformations, and therapeutic outcome, could be documented. Moreover, RPS19 mutations were also found in some first-degree relatives presenting only with isolated high erythrocyte adenosine deaminase activity and/or macrocytosis. The lack of a consistent relationship between the nature of the mutations and the clinical phenotype implies that yet unidentified factors modulate the phenotypic expression of the primary genetic defect in families with RPS19 mutations.

Adenosine deaminase (ADA) activity and isozymes in the serum of patients with hepatitis B compared with healthy people: a useful method in diagnosis clinical status

Background: Adenosine deaminase (ADA) specifications (EC3.5.4.4) is an enzyme is involved in purine metabolism that breaks adenosine and deoxy-adenosine and produce inosine and deoxy-inosine and ammonia. The highest levels are of adenosine deaminase activity in monocytes and lymphocytes. High serum ADA activity with increased serum levels of AST, ALT and immunoglobulins were reported in variety of diseases including hepatitis. We aimed to investigate the activity of total ADA in serum of patients with hepatitis B and were determined molecular weight ADA1 and ADA2 isozymes in serum and RBC of hepatitis patients. Materials and Methods: We were defining experiments by electrophoresis on SDS-PAGE, for isozymes of ADA; ADA1 and ADA2 in serum and red blood cells. ADA1 molecular weight was estimated at about 35 KDa and ADA2 about 110 KDa. The total ADA activity was measured by the modified Ellis method in 37 patients with hepatitis B and 40 healthy controls in the age range (20-60 years). Results: The normal values for serum ADA in humans have been studied by various workers and found in serum samples to be in the range of 0-15 U/L, whiles in our analysis total ADA (tADA) enzyme activity is in controls and patients with hepatitis B, respectively, 13.35 ± 1.62 and 27.05 ± 8.49. Our results indicated that tADA level was higher in patients with hepatitis B than those of corresponding controls (P < 0.05).Total ADA enzyme activity shows a significant increase compared to the control group in all age groups tested. Conclusion: Therefore, the serum ADA level could be used as an index along with other parameters in follow up of patients with hepatitis B.

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.

Adenosine deaminase activity in metabolically healthy obese and metabolically un healthy obese individuals in relation to metabolic syndrome

Obesity is a major worldwide health problem leading to markedly increased mortality and serious morbidity. Literature demonstrates high Adenosine deaminase activity in overweight and obesity than non-obese individuals. It was known that obesity is not a homogenous but it was heterogeneous like metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). Accordingly we have undertaken a preliminary comparative study to estimate the adenosine deaminase activity in metabolically healthy and unhealthy subjects and its clinical significance in predicting the pathogenesis of obesity at an early stage. A group of 47 adult obese subjects having increased waist circumference [males >90cm, females >80cm] were selected. A group of 40 age and sex matched healthy individuals were served as controls. Serum Adenosine deaminase activity and parameters of modified NECP APT III criteria of metabolic syndrome were performed in all the subjects. Based on the metabolic syndrome risk factors the obese subjects were grouped into metabolically healthy and metabolically unhealthy subjects. Waist circumference was taken as common metabolic risk factors in both the groups. Comparison of metabolically healthy vs. unhealthy, control vs. metabolically healthy and metabolically healthy vs. control was done. Finally Pearson’s correlation of number of metabolic syndrome risk factors and adenosine deaminase activity was done. All metabolic syndrome parameters were significantly elevated in obese individuals. The mean ADA in obese (35.93±17.76) was significantly elevated than controls (19.98±3.41). In metabolically healthy subjects the mean ADA was found to be 17.82±5.22 whereas it was 46.2±13.70 in metabolically unhealthy obese subjects. Pearson’s correlation of number of metabolic syndrome risk factors against adenosine deaminase showed positive correlation and it was statistically significant (r=0.6524 p=0.0001). Elevated adenosine deaminase activity in metabolically healthy obese individuals may predict immunopathological transition of healthy obese to metabolically unhealthy.

Optimal Cutoff Value of Serum Adenosine Deaminase Activity for Diagnosing Acute Scrub Typhus

The objective of this study was to determine the optimal cutoff value of serum adenosine deaminase (ADA) activity for diagnosing scrub typhus in acute febrile patients, especially in the autumn. A total of 715 febrile patients were included; 286 of them were diagnosed with acute scrub typhus. The mean serum ADA activities in patients with and without scrub typhus were 42.8 ± 13.4 IU/L and 17.2 ± 11.5 IU/L, respectively. The optimal cutoff value for serum ADA activity was determined to be 25.0 IU/L with a sensitivity of 92.3%, specificity of 86.6%, and area under the curve of 89.4% using a receiver-operating characteristic curve analysis. The possibility of scrub typhus must be considered when acute febrile patients present with high ADA activity (>25 IU/L), especially in the autumn. Determining the optimal serum ADA activity cutoff value may help clinicians diagnose acute scrub typhus prior to serological confirmation.

Evaluation of Nested Polymerase Chain Reaction for Rapid Diagnosis of Clinically Suspected Tuberculous Pleurisy

Early diagnosis of tuberculosis is important in its control. The conventional techniques like smear microscopy and culture suffer from low sensitivity for diagnosis of extra-pulmonary tuberculosis like Pleural Tuberculosis (PTB) due to paucibacillary nature of the fluid. Polymerase Chain Reaction (PCR) is presently seen as a promising alternative to conventional techniques. In this study we have evaluated IS6110 sequence based nested PCR (nPCR) for the detection of Mycobacterium tuberculosis (MTB) DNA directly from clinical samples. The results of PCR were compared with the results of conventional methods like smear, culture and Adenosine Deaminase (ADA) activity. A total of 50 pleural fluid samples from the patients with history suggestive of tuberculosis were taken. All the samples were processed for Ziehl-Neelsan (ZN) staining for Acid Fast Bacilli (AFB), culture ADA activity and PCR with primers targeting 123bp fragment of IS6110 of MTB complex. A significant difference was seen in the sensitivities of conventional methods and PCR (p<0.05). Out of these 50 samples 3 were positive by smear, culture was positive in 5 samples, 21 samples showed high ADA activity and 29 were positive by PCR with overall 100% sensitivity of PCR using culture on LJ media as gold standard. The combined analysis of nPCR, ADA activity and other lab investigations can be very useful in the rapid diagnosis in cases of PTB.

Is adenosine deaminase in pleural fluid a useful marker for differentiating tuberculosis from lung cancer or mesothelioma in Japan, a country with intermediate incidence of tuberculosis?

The objective of this study was to evaluate the utility of the determination of adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in Japan, a country with intermediate incidence of tuberculosis (TB). We retrospectively reviewed the clinical records of 435 patients with pleural effusion and investigated their pleural ADA levels as determined by an auto analyzer. ROC analysis was also performed. The study included patients with MPE (n＝188), TPE (n＝124), benign nontuberculous pleural effusion (n＝94), and pleural effusion of unknown etiology (n＝29). The median ADA level in the TPE group was 70.8U/L, which was significantly higher than that in any other groups (p＜0.05). The area under the curve (AUC) in ROC analysis was 0.895. With a cut-off level for ADA of 36U/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.5%, 86.5%, 69.7%, and 93.6%, respectively. As many as 9% of patients with lung cancer and 15% of those with mesothelioma were false-positive with this ADA cutoff setting. Although the ADA activity in pleural fluid can help in the diagnosis of TPE, it should be noted that some cases of lung cancer or mesothelioma show high ADA activity in geographical regions with intermediate incidence of TB, in contrast to high prevalence areas.

A case of isoniazid-resistant miliary tuberculosis in which tuberculous meningitis paradoxically developed despite systemic improvement

A 63-year-old man with chronic myelomonocytic leukemia was admitted to our hospital with miliary tuberculosis. He received anti-tuberculosis drugs: isoniazid (INH), rifampicin (RFP), ethambutol (EB), and pyrazinamide (PZA). His condition clearly and immediately improved after the therapy, but he experienced a high fever of about 38°C every day from 1month after the initiation of the therapy. Drug-induced fever and tumor fever were suspected as causes, but the etiology could not be determined. The tuberculosis was identified as an INH-resistant strain, so INH was stopped and levofloxacin (LVFX) was introduced, with streptomycin (SM), in addition to RFP, EB, and PZA. At 2months after the initiation of the therapy (about one week after the change in the anti-tuberculosis drug regimen), his spinal fluid was examined, given his complaints of headache and vomiting. The spinal fluid analysis revealed invasion of lymphocytic inflammatory cells and high adenosine deaminase activity; the patient was thus diagnosed with tuberculous meningitis. His condition gradually improved after the changing of the anti-tuberculosis drugs. Thus, to summarize, the tuberculous meningitis had worsened paradoxically despite his systemic improvement, although it was successfully treated by the addition of LVFX and SM. We must keep in mind that a potential cause of fever during anti-tuberculosis therapy may be INH-resistant tuberculous meningitis.

Diagnostic performance of adenosine deaminase activity in pleural fluid: A single-center experience with over 2100 consecutive patients

Objective To determine the diagnostic utility of adenosine deaminase (ADA) in a large series of pleural effusions of different etiologies. Methods A retrospective study of 2104 consecutive patients presenting with pleural effusion was carried out at a Spanish university hospital. ADA levels in pleural fluid were determined using a non-Giusti automatic kinetic assay, and a receiver operating characteristics curve analysis was applied to estimate their discriminative properties. Results Pleural tuberculosis (TB) accounted for 221 (10.5%) effusions. Pleural fluid ADA > 35 U/L yielded 93% sensitivity, 90% specificity, a positive likelihood ratio (LR) of 10.05 and a negative LR of 0.07 for the diagnosis of TB among lymphocytic exudates. The ADA activity was significantly higher in neutrophil- (111.6 U/L) than in lymphocyte-rich (62.4 U/L; p = 0.002) TB effusions. Overall, more than 40% of parapneumonics and half of lymphomatous effusions exceeded the cutoff set for TB. These were the only causes of ADA activity above 250 U/L. When the prevalence of TB as a cause of exudative effusions is low (e.g., 1%), the estimated positive predictive value of the ADA test may be as low as 7%, although the negative predictive value remains high (99.9%). Conclusion Where available, pleural ADA should be routinely used to rule TB in or out in areas with moderate to high or low TB prevalence, respectively. A high ADA level is a characteristic not only of lymphocytic, but also of neutrophilic TB effusions. An extremely high ADA activity should raise suspicion of empyema or lymphoma.

Tuberculous peritonitis in cirrhotic patients: Comparison of spontaneous bacterial peritonitis caused by Escherichia coli with tuberculous peritonitis

The aim of this study was to compare the characteristics of tuberculous peritonitis (TP) and spontaneous bacterial peritonitis (SBP) in cirrhotic patients. In a retrospective review of the medical records of a single tertiary hospital between 1988 and 2006, 15 patients met the diagnostic criteria TP and liver cirrhosis. For comparison, we randomly selected 3 cirrhotic patients with SBP caused by Escherichia coli for each cirrhotic patient with TP. Compared to SBP, TP in cirrhotic patients was more frequently associated with extra-peritoneal tuberculosis (TP vs SBP: 53.3% vs 0%), an insidious onset (> or =2 weeks; 60% vs 2.2%), and Child-Pugh classification class B at onset (80% vs 8.9%) (p<0.05). Compared to SBP, TP was associated with lower white blood cell count in ascites (TP vs SBP: 2.0+/-2.2 x 10(3)/mm(3) vs 7.2+/-7.5 x 10(3)/mm(3)), a higher proportion of mononuclear leukocytes (lymphocytes and monocytes) in ascites (88.9+/-9.5% vs 16.6+/-15.3%), higher protein concentration in ascites (3.1+/-1.7 g/dl vs 1.2+/-0.3 g/dl), and higher adenosine deaminase activity in ascites (62.3+/-31.8 U/l vs 6.9+/-3.1 U/l) (p<0.05). TP should be suspected in cirrhotic patients with relevant clinical manifestations and characteristics of ascites.

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

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.

Adenosine Deamination Sustains Dendritic Cell Activation in Inflammation

Adenosine is a suppressive agent that protects the host from excessive tissue injury associated with strong inflammation. In tissue stress, higher levels of adenosine signal through adenosine receptors to exert strong anti-inflammatory effects, and thus protect host cells. Existing evidence also suggests that elevated adenosine potently down-regulates the activation of lymphocytes during inflammation. This notion, however, is in contrast with another basic observation that the immune system is highly activated precisely under the same circumstances against pathogens. In this study, we show that inflammatory responses of dendritic cells (DCs) are highly sensitive to adenosine suppression. However, they intrinsically carry high adenosine deaminase activity, which in turn degrades and removes adenosine from the surroundings, cutting off DCs from the suppression. This regulatory mechanism is important in DC responses to pathogen-associated molecular patterns and their activation of T cells. Our findings suggest a mechanism that DCs maintain their hyperreactive state in inflammation despite the general state of suppression, and reveal a regulatory role of adenosine deaminase in DC innate immune responses.

Serum and erythrocyte adenosine deaminase activities in patients with Behçet's disease

Adenosine deaminase (ADA) is a non-specific marker of the activation of the T cell, which has an important role in the etiology of Behçet's disease (BD). The purpose of this study was to investigate the determination of ADA activity as an index of T-lymphocyte function in BD, which is known to have an T-cell-mediated immune response. Adenosine deaminase activities in both serum and erythrocytes were measured in 23 untreated patients with BD and in 20 healthy controls. The patients with BD were divided into two groups: active (n = 10) and inactive (n = 13). When compared with the control group, serum ADA activity was high (P < 0.01) and erythrocyte ADA activity was significantly low (P < 0.01) in BD. Serum ADA activity of active BD was higher than that of inactive BD (P < 0.01), but erythrocyte ADA activity was found to be lower in active BD than inactive BD (P < 0.01). These findings may provide an additional benefit for the diagnosis of BD and sub-typing of active and inactive BD.

Type 2 diabetes and the genetics of signal transduction: A study of interaction between adenosine deaminase and acid phosphatase locus 1 polymorphisms

Acid phosphatase locus 1 (ACP1) is a highly polymorphic enzyme that has an important role in flavoenzyme activity and in the control of insulin receptor activity and band 3 protein phosphorylation status. Adenosine deaminase (ADA) is a polymorphic enzyme that catalyses the irreversible deamination of adenosine to inosine and has an important role in regulating adenosine concentration. Based on the hypothesis that ACP1 counteracts insulin signaling by dephosphorylating the insulin receptor and that adenosine has an anti-insulin action, we reasoned that low ACP1 activity (low dephosphorylating action on insulin receptor) when associated with high ADA activity (low adenosine concentration) would result in a cumulative effect towards an increased glucose tolerance. On the contrary, high ACP1 activity when associated with low ADA activity would result in a cumulative effect towards a decreased glucose tolerance. A total of 280 adult subjects with type 2 diabetes from the population of Penne (Italy) were studied. There was a nonsignificant trend toward an increase in the proportion of subjects with the complex type with high ACP1 activity and low ADA activity (ie, ∗B/∗B; ∗A/∗C; ∗B/∗C; ∗C/∗C//ADA∗1/∗2 and ∗2/∗2) in type 2 diabetes relative to that observed in newborn infants from the same population. High ACP1 activity/low ADA activity joint genotype was positively associated with high glycemic levels and with high body mass index (BMI) values. Low ACP1 activity/high ADA activity joint genotype was also positively associated with dyslipidemia. These findings suggest that both ACP1 and ADA contribute to the clinical manifestations of type 2 diabetes and probably also have a marginal influence on susceptibility to the disease. Both additive and epistatic interactions between the 2 systems seem to be operative.

A Case of Mycoplasma Pneumoniae Pneumonia Accompanying High Adenosine Deaminase Activity in Pleural Effusion

Mycoplasma pneumioniae has a unique genomic composition, cellular biology, and a fastidious nature as the smallest cell-free living organism that lacks a cell wall. Previous studies have suggested that a clinical manifestation of a M. pneumoniae infection is a consequence of a host immune response, particularly involving cellular immunity. Adenosine deaminase (ADA) is the main T-lymphocyte enzyme, and its activity is high in diseases where cellular immunity is stimulated. Therefore, its activity is useful for diagnosing a tuberculous pleural effusion. A pleural effusion is found in 5-20% of Mycoplasma pneumonia patients. However, there are few reports of high ADA activity in a mycoplasmal pleural effusion. Here we report a case of Mycoplasma pneumoniae infection established by a polymerase chain reaction and serologic tests, accompanying high ADA activity in a pleural effusion.