The Utility of Pleural Fluid Cell IFN-γ Production Assay in the Diagnosis of Tuberculous Pleurisy

Background : Diagnosis of tuberculous pleurisy is sometimes difficult using conventional diagnostic methods. We have investigated the utility of pleural fluid cell $IFN-{\gamma}$ production assay in the diagnosis of tuberculous pleurisy. Methods : We prospectively performed pleural fluid cell $IFN-{\gamma}$ production assay in 39 patients with tuberculous pleural effusions (TPE) and in 26 patients with nontuberculous pleural effusions (NTPE) (13 malignant pleural effusions and 13 parapneumonic effusions). Pleural fluid cells were cultured in DMEM media and stimulated with purified protein derivatives (PPD), and phytohemagglutinin (PHA) for 24 hr. The amount of $IFN-{\gamma}$ released in the culture supernatant was quantitated by $IFN-{\gamma}$ ELISA assay. We have also measured adenosine deaminase (ADA) activities and $IFN-{\gamma}$ concentrations in the pleural fluid. Results : 1) The pleural fluid levels of ADA activity and $IFN-{\gamma}$ concentrations were significantly higher in TPE than NTPE (p<0.01). 2) $IFN-{\gamma}$ production in TPE cells stimulated by PPD ($755,266{\pm}886,636pg/ml$) was significantly higher than NTPE cells ($3,509{\pm}6,980pg/ml$) (p<0.01). By considering the fact that $IFN-{\gamma}$ concentrations over 10,000 pg/ml is a criteria for the diagnosis of TBE, sensitivity and specificity of the test were 97.4 and 92.3%, respectively. 3) The ratios of $IFN-{\gamma}$ production by the stimulation with PPD and PHA (PPD/PHA) were significantly higher in TPE cells ($59{\pm}85$) than NTPE cells ($5{\pm}18$)(p<0.01). Considering the criteria for the diagnosis of TBE as PPD/PHA ratio over 5, sensitivity and specificity of the test were 76.9 and 92.3%, respectively. Conclusion : Pleural fluid cell $IFN-{\gamma}$ production assay may be useful for the diagnosis of tuberculous pleurisy.

결핵성 흉막염의 진단에서 결핵균 항원 자극에 의한 흉수 세포의 IFN-γ 분비 검사의 유용성

연구배경 : 결핵균 항원자극에 의한 흉수 세포의 $IFN-{\gamma}$ 분비검사가 결핵성 흉막염과 다른 원인의 흉수의 감별진단에 유용한지 알아보고자 하였다. 방 법 : 39명의 결핵성 흉막염 환자와 비결핵성 흉수를 보인 26명의 환자(부폐렴성 흉수 13명, 암성 흉수 13명)들의 흉수세포를 분리하여 배양하면서 PPD와 PHA로 24시간 자극한 후 배양상층액의 $IFN-{\gamma}$ 농도를 ELISA 방법으로 측정하였다. 결 과 : 1) 결핵성 흉수의 ADA 활성도 및 $IFN-{\gamma}$ 농도는 비결핵성 흉수보다 높았다(p < 0.01). 2) PPD로 흉수세포들을 자극하였을 때 분비되는 $IFN-{\gamma}$ 농도는 결핵성 흉수($755,266{\pm}886,636pg/ml$)에서 비결핵성 흉수($3,509{\pm}6,980pg/ml$)보다 높았다(p<0.01). 결핵성 흉막염의 진단기준을 $IFN-{\gamma}$ 농도가 10,000 pg/ml 이상인 경우로 정의하였을 경우 민감도는 97.4%, 특이도는 92.3%였다. 3) PPD 자극에 의한 흉수세포의 $IFN-{\gamma}$ 분비를 PHA로 자극하였을 때의 $IFN-{\gamma}$ 분비에 대한 비로 비교하였을 때 결핵성 흉수($59{\pm}85$)에서 비결핵성 흉수($5{\pm}18$)보다 높았다(p<0.01). 결핵성 흉막염의 진단기준을 PPD/PHA 비가 5이상인 경우로 정의하였을 경우 민감도는 76.9%, 특이도는 92.3%였다. 결 론 : 결핵균 항원 자극에 의한 흉수세포 $IFN-{\gamma}$ 분비검사는 결핵성 흉막염의 진단에 이용될 수 있을 것이다.