HSP65在结核病血清学诊断中的应用前景初探

Study on Serum Mycobacterial HSP65-Specific IgG as a Potential Diagnostic Biomarker for Active Tuberculosis

及时准确的诊断对结核病的防控至关重要。虽然简易快速的血清学检测技术在病毒等感染性疾病的诊断中得到广泛应用,但目前临床上结核病的血清学诊断技术尚不理想。我们通过间接ELISA方法比较筛查多个结核分枝杆菌抗原在正常人和活动期结核病患者中的血清学应答水平,发现结核分枝杆菌抗原HSP65(Rv0440)的特异性IgG水平在活动期结核病患者外周血浆中明显高于健康对照组(P<0.0001),其检测的灵敏度达90%,特异性达90%,ROC曲线的AUC值达0.978,上述指标均与目前临床上使用的抗38kD(Rv0934)蛋白的IgG水平相当;同时结合结核病患者临床资料分析结果显示抗HSP65的IgG在空洞病变结核病患者中的平均水平显著高于无空洞患者;部分抗38kD IgG抗体阴性的结核病患者中抗HSP65IgG抗体水平呈现阳性,提示抗HSP65IgG可以成为目前商业化抗38kD IgG检测的补充,从而进一步提高结核病诊断的灵敏度。上述研究结果表明抗HSP65IgG抗体有望成为诊断活动期结核病的候选补充血清标志物。

Tuberculosis （TB） remains a major health problem worldwide. Rapid and accurate diagnosis is critical for prevention and treatment of the disease. Until now there are few biomarkers for successful serological diagnosis in clin- ic. Here,through screening serum IgG levels against multiple Mycobacterium tuberculosis （M. tb）-derived antigens by ELISA,we found that anti-HSP65 IgG antibody level elevated dramatically in the serum of active TB patients when compared to those of healthy controls （P^0. 0001）. The sensitivity of the test was 900/oo whereas the specificity was 90 ~, which was similar to a commercially-used antigen 38kD. In a receiver operating characteristic （ROC） analysis, ser um anti-HSP65 IgG level had comparable area under the curve （0. 978） to that of 38 kD antigen （0. 982）. More inter estingly,cavitary TB patients showed a significant increase of anti-HSP65 IgG in the serum compared to non-cavitary patients. Patients with anti-38kD IgG negative responses exhibited positive responses against HSP65, which indicated its supplementary role to the present diagnosis index. Our results thus imply the potential of anti-HSP65 IgG as a novel serological diagnostic biomarker for active TB.