Tuberculous Effusion: ADA Activity Correlates with CD4+ Cell Numbers in the Fluid and the Pleura

Abstract

Background: Adenosine deaminase (ADA) is a commonly used marker in the diagnosis of tuberculous effusion and there is evidence that its production is linked to T cells and monocytes. Data on the correlation between ADA and T cells or macrophages in tuberculous effusions are conflicting. Furthermore, no studies have examined a possible correlation between pleural tissue infiltration and ADA. Objectives: We undertook this study to examine cell subsets in the fluid and the pleura in tuberculous effusion and their correlation to ADA. The use of cell subsets as a marker in the differential diagnosis was also examined. Methods: Pleural fluid from 36 patients with tuberculous and 34 patients with malignant effusion as well as pleural tissue biopsies from 16 patients with tuberculous pleurisy were examined. The APAAP and the avidin-biotin complex immunocytochemical methods were used to examine CD4+ T cells and macrophages (CD68+), while ADA activity was measured by the Giusti colorimetric method. Results: Our results showed that, in pleural fluid, CD4+ cells and ADA were significantly higher in tuberculous compared to malignant effusion (p < 0.001 for all measurements). In pleural tissue biopsies, macrophages were the predominant cells but CD4+ T cells were also abundant. A significant correlation was found between ADA and CD4+ numbers in pleural fluid and tissue (r = 0.45, p < 0.01; r = 0.75, p < 0.001, respectively). ADA had high sensitivity and specificity for differential diagnosis while cell subsets did not. Conclusions: These results indicate that ADA activity correlates to CD4+ T cell infiltration in the pleura and the fluid. Moreover, ADA but no cell subsets may be used as markers of tuberculous effusion.

Clinical and Laboratory Parameters in the Differential Diagnosis of Pleural Effusion Secondary to Tuberculosis or Cancer

“…The next step is the quantification of ADA, an enzyme produced by macrophages and activated T lymphocytes, 18 which is usually elevated in tuberculosis. In this situation, the activity of the enzyme is generally higher than 40 U/ L, although similar levels are observed in lymphocytic pleural effusions secondary to rheumatoid arthritis and certain lymphoproliferative diseases.…”

Novel tests for diagnosing tuberculous pleural effusion: what works and what does not?

“…In one study, although pleural fluid ADA activity correlated with the number of CD4+ T-cells in the pleural space [38], the number of pleural CD4+ cells was not an accurate diagnostic test for TB.…”

Tuberculose pleural

“…(15) Um estudo recente revelou uma correlação entre a atividade da ADA e o alto número de células CD4 no líquido pleural de pacientes com TB, comparados a pacientes com câncer. (16) Em diferentes estudos de diagnóstico de derrame pleural, a ADA demonstrou sensibilidade de 90% a 100% e especificidade de 89% a 100%, quando se utilizou valor de corte maior que 40 U/l. A ADA pode apresentar resultados falso positivos em alguns tipos de linfoma, na artrite reumatóide, no lúpus, em alguns adenocarcinomas e no empiema.…”

“…Entretanto, a história clínica, a análi-se de imagem e a evolução clínica permitem que estes casos sejam mais facilmente discriminados. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) Com base nestas constatações, recomenda-se a pesquisa rotineira da ADA para o diagnóstico da tuberculose pleural.…”