Adenosin deaminasa como molécula coestimuladora y marcador de inmunidad celular / Adenosine deaminase as costimulatory molecule and marker of cellular immunity

La adenosin deaminasa (ADA), es una enzima del metabolismo de las purinas que ha sido objeto de mucho interés debido a que el defecto congénito de esta enzima causa el síndrome de inmunodeficiencia combinada severa. Una de las tres isoformas de la enzima (ecto-ADA) es capaz de unirse a la glicoproteína CD26 y a los receptores de adenosina A1 y A2B. La interacción ADA-CD26 produce una señal coestimuladora en los eventos de activación de las células T y en la secreción de IFN-g, TNF-a e IL-6. Durante dicha activación la actividad de la enzima está regulada de manera positiva por IL-2 e IL-12 y negativamente por IL-4, basado en un mecanismo de translocación. Diversos estudios señalan que los niveles séricos y plasmáticos de ADA se elevan en algunas enfermedades causadas por microorganismos que infectan principalmente a los macrófagos; así como en trastornos hipertensivos, lo cual podría representar un mecanismo compensatorio como consecuencia de la elevación de los niveles de adenosina y la liberación de mediadores hormonales e inflamatorios estimulados por la hipoxia.

Adenosine deaminase (ADA) is an enzyme of purine metabolism which has been the subject of much interest because the congenital defect of this enzyme causes severe combined immunodeficiency syndrome. One of the three isoforms of the enzyme (ecto-ADA) is capable of binding to the glycoprotein CD26 and adenosine receptors A1 and A2B. ADA-CD26 interaction produces a costimulatory signal in the events of T cell activation and secretion of IFN-g, TNF-a and IL-6. During this activation, the enzyme activity is regulated positively by IL-2 and IL-12 and negatively by IL-4, based on the mechanism of translocation. Diverse studies suggest that seric and plasmatic levels of ADA rise in some diseases caused by microorganisms infecting mainly the macrophages and in hypertensive disorders, which may represent a compensatory mechanism resulting from increased adenosine levels and the release of hormones and inflammatory mediators estimulated by hipoxia.

Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2) in schizophrenic patients / Diminuição da frequência da variante alélica de baixa atividade da adenosina desaminase (ADA1*2) em pacientes esquizofrênicos

OBJECTIVE: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A) (ADA1*2) exhibits 20-30 percent lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2) in schizophrenic patients and healthy controls. METHOD: The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. RESULTS: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6 percent) relative to controls (13/111 - 11.7 percent, p = 0.032, OR = 2.6). CONCLUSION: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients.

OBJETIVO: A adenosina pode ter um papel importante na fisiopatologia da esquizofrenia, uma vez que modula a liberação de vários neurotransmissores, tais como glutamato, dopamina, serotonina e acetilcolina, diminui a atividade neuronal por hiperpolarização pós-sináptica e inibe a atividade dopaminérgica. A adenosina desaminase participa do metabolismo das purinas pela conversão de adenosina em inosina. O mais frequente polimorfismo funcional da adenosina desaminase (22G →A) (ADA1*2) exibe uma diminuição de 20-30 por cento da atividade funcional em indivíduos com genótipo G/A quando comparados com indivíduos com o genótipo G/G. O objetivo deste estudo foi avaliar o polimorfismo 22G→A (ADA1*2) em pacientes esquizofrênicos e em controles saudáveis. MÉTODO: Os genótipos da ADA 22G →A foram identificados através de uma estratégia de PCR alelo-específica em 152 pacientes esquizofrênicos e 111 controles saudáveis. RESULTADOS: Foi observada uma diminuição significativa na frequência do genótipo G/A em pacientes esquizofrênicos (7 - 4,6 por cento) em relação ao grupo controle (13 - 11,7 por cento, p = 0,032, OR = 2,6). CONCLUSÃO: Estes resultados sugerem que o genótipo G/A associado com baixa atividade de adenosina desaminase, e potencialmente com níveis aumentados de adenosina, é menos frequente entre pacientes esquizofrênicos.

Erythrocytic adenosine deaminase activity in combined immunodeficiency disorders

Severe combined immunodeficiency [SCID] due to adenosine deaminase [ADA] deficiency is a rare autosomal recessive disorder that leads to early demise of the affected child. In this study, we examined the active of ADA in 8 egyptian families with [SCID] be estimating erythrocytic ADA levels in family members as we as 15 healthy subjects as a control. Noreover, we examined the ADA enzyme kinetics [km, thermal stability and ph profile] in residual activity of affected and healthy subjects to characterize its mutations. The erythrocytic ADA activity were low in 2 clinically affected cases and in 11 out of 15 [73%] obligate heterozygotes. Using enzyme kinetics studies, more than one mutation type could be delineated: a] reduced enzyme activity and substrate affinity with normal thermostability b] a thermolabile enzyme with reduced activity, with normal affinity to substrate. c] normal enzyme activity but with reduced affinity to substrate. In sconclusion, we reconfirmed the validity of the assay of erythrocytic ADA in detecting a high percentage of heterozygous state among suspected carriers. In addition, we defined the biochemical criteria of the detected mutations

Adenosindeaminasa como método diagnóstico en tuberculosis pleural

Estudiamos 128 pacientes con derrame pleural, a los cuales se les realizó un diagnóstico histológico o bacteriológico definitivo. La medición del ADA en líquido pleural separó claramente los grupos de tuberculosis y neoplasia con un punto de corte de 36U. Teniendo una sensibilidad de 97.59 por ciento y un valor predictivo negativo de un 94.8 por ciento.

Adenosine deaminase activity in bronchoalveolar lavage of pulmonary tuberculosis

Adenosine deaminase [ADA] activity, lymphocytes and T-cell subsets% [CD3%, CD4% and CD8%] were measured in BAL from 15 patients with active pulmonary TB, 15 persons with inactive pulmonary TB and 15 normal nonsmoker volunteers. ADA activity in BAL and serum, lymphocytes%, CD3%, CD4% and CD4: CD8 ratio in BAL were statistically highly significantly [p <0.001] increased among patients with active pulmonary TB compared with inactive cases and normal controls, whereas no statistical difference [p >0.05] was found as regard CD8%. ADA activity showed positive correlation more with CD4% in BAL [r = +0.93] and both showed positive correlation with tuberculin test. So, ADA may constitute a new marker of cell-mediated immune response and tuberculous lung infection is characterized by T- cell [CD4] alveolitis. It is suggested that, ADA activity in BAL over 3 U/L and/or serum: BAL ADA ratio below 7, BAL lymphocytes >10%, CD3 >50% or CD4: CD8 ratio >2.5 denoted active pulmonary TB, whereas lower values serve to diagnose inactive disease. So, measurement of ADA activity and T-cell subsets% in BAL may be valuable parameters for diagnosis and follow up of pulmonary TB