探討 interferon gamma 以及 interferon gamma inducible protein-10 做為肺結核診斷以 及 治 療 的 潛 在 性 生 物 指 標 的 可 行 性

Abstract

Objective： In our previous research (Latent infection among close contacts of multidrug-resistant tuberculosis patients in central Taiwain, 2008), we used an IGRA (QFT-GIT) to examine the contactors of tuberculosis. However, IGRAs cannot differentiate active or latent tuberculosis infection, nor the outcome of treatment. Therefore, may studies have been designed with a combination of IGRA examinations of IGRAs and other cytokines, such as IP-10, IL-2 and IFN-γ. Recently, the serum level of IP-10 (INF- γ inducible protein – 10 ) has been proposed a new biomarker to detect tuberculosis infection. Methods： We chose the new cases of pulmonary tuberculosis and MDR-TB and obtain blood samples for IGRA and IP-10. We divided these patients into the three groups: 1.those with pulmonary tuberculosis ; 2. those with MDR-TB; and 3. healthy controls. The inclusion criteria were newly diagnosed TB and MDRTB MDRTB those who had not received the anti-Tb treatment, or persistently positive findings on sputum acid – fast staining . The exclusion criteria were an age less than 18 years, negative sputum acid – -fast staining before the use of second-line anti- TB drugs, those who were HIV positive and hemodialysis patients. (Table 1) Blood samples for IP-10 and IGRA were collected at baseline before anti-TB treatment. We also collected blood samples in the second week, second month and the six month after anti-TB treatment .(Figure 3) We compared the IGRA and IP-10 data during the anti-TB treatment course compared with conventional sputum samples. and IP-10 level data. Results： There were 30 healthy controls, 17 patients with MDR-TB (resistant to INH and RMP), and 20 patients with TB (Table1). During the course of the treatment, there was no significant difference in IP-10 level between the two therapy groups (the MDR –TB and TB groups). The IP-10 level were also not revealed compatible variation between the 2 therapy groups. The average IP-10 data was 131.94±102.83pg/ml in the control group (healthy persons), 458.71±301.90pg/ml in the TB group, and 513.66±279.80pg/ml in the MDR-TB group. According to these data, the IP-10 level was obviously more decreased than the therapy groups. In the control group, only 2 persons had the elevated IP-10 levels. However, one of them was also receiving hepatitis C treatment, the other was the sitter in the isolation room. In the therapy group, the average IP-10 level was declined at 2 weeks, 2 months and 6 months after treatment. Compared with positive findings of sputum smears and cultures, the average IP-10 level was 544.05pg/ml in the patients with positive sputum smears and cultures, and average IP-10 level was 397.44pg/ml in the patients with negative finding of sputum smear and culture.(Figure 4.) We found that the IGFA and IP-10 level were both declined in the treatment group when theses patients received the anti-TB drugs. However, we also observed that the treatment response was not compatible with the variation in biomarkers level. For example, when IGRA was positive , the average IP-10 level was 86.19pg/ml to 1066.58pg/ml. However, when IGRA was negative , the average IP-10 level was 90.03pg/ml to 1041.74pg/ml. This result is similar to the study by Theron in South Africa and suggest that the IGRA level did not obviously correlate with the anti-TB treatment during different stages of the treatment. (Figure 5, 6-1, 6-2, 6-3, 6-4 ) Conclusion: The average IP-10 level in the therapy group was far lower than in the controls. The value of IP-10 was investigated as a method to detect TB infection and to enhance the screening of the TB cases. We also observed that the IP-10 values in the TB group did not correspond with those in the MDR-TB group. This may be because the presentation of antigens or antibodies different and it was therefore difficult to analyze the IP-10 data. Therefore, IP-10 was not a biomarker of the indicators of outcome of the TB treatment.