DST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 19063, Tygerberg 7505, South Africa; Lionex Diagnostics and Therapeutics, 38126 Braunschweig, Germany.
Lionex Diagnostics and Therapeutics, 38126 Braunschweig, Germany.
J Infect. 2014 Dec;69(6):581-9. doi: 10.1016/j.jinf.2014.05.014. Epub 2014 Jun 23.
Accurate, simple and cost-effective diagnostic tests are needed for diagnosis of active tuberculosis (TB). Serodiagnosis is attractive as it can be harnessed for point-of-care tests.
We evaluated, in a blinded fashion, the sensitivity and specificity of serologic immunoglobulin (Ig)G, IgA and/or IgM responses to Apa, heat shock protein (HSP) 16.3, HSP20, PE35, probable thiol peroxidase Tpx and lipoarabinomannan (LAM) in 42 HIV-negative South African pulmonary TB patients and 67 control individuals. The status of latent Mycobacterium tuberculosis infection (LTBI) among controls was defined through the TST and IFN-γ release assays (IGRAs). We evaluated 47 definite LTBI (IGRA(+)/LTBI), 8 putative LTBI (IGRA(-)/TST(+)) and 12 TB-uninfected (non-LTBI) subjects.
In contrast to anti-PE35 IgA, anti-PE35 IgG and particularly anti-Apa IgA, performances of anti-LAM IgG and selected anti-protein antibodies were less affected by inclusion of LTBI participants into the analysis. Anti-LAM IgG showed with a sensitivity/specificity of 71.4%/86.6% (p < 0.001) the best discrimination between TB and non-TB subjects. Selected five-antibody-combinations (including anti-LAM IgG, anti-LAM IgA and anti-Tpx IgG) further improved this performance to an accuracy exceeding 86%.
Antibody responses to some Mycobacterium tuberculosis antigens often also reflect latent infection explaining the poor performance of antibody-based tests for active TB in TB-endemic settings. Our results suggest that rather a combination of serological responses against selected protein and non-protein antigens and different Ig classes should be investigated for TB serodiagnostics.
需要准确、简单且具有成本效益的诊断测试来诊断活动性肺结核（TB）。血清诊断具有吸引力，因为它可以用于即时检测。
我们以盲法方式评估了针对 Apa、热休克蛋白（HSP）16.3、HSP20、PE35、可能的硫氧还蛋白 Tpx 和脂阿拉伯甘露聚糖（LAM）的免疫球蛋白（Ig）G、IgA 和/或 IgM 反应在 42 名 HIV 阴性南非肺结核患者和 67 名对照个体中的敏感性和特异性。对照者潜伏性结核分枝杆菌感染（LTBI）的状态通过 TST 和 IFN-γ 释放试验（IGRAs）定义。我们评估了 47 例明确的 LTBI（IGRA(+)/LTBI）、8 例疑似 LTBI（IGRA(-)/TST(+)) 和 12 例 TB 未感染（非 LTBI）个体。
与抗-PE35 IgA 相反，抗-PE35 IgG 和特别是抗-Apa IgA，抗-LAM IgG 和选定的抗蛋白抗体的性能受纳入 LTBI 参与者到分析中的影响较小。抗-LAM IgG 显示出 71.4%/86.6%（p < 0.001）的敏感性/特异性（p < 0.001），在区分 TB 和非 TB 受试者方面表现最佳。选定的五种抗体组合（包括抗-LAM IgG、抗-LAM IgA 和抗-Tpx IgG）进一步提高了这种性能，准确性超过 86%。
针对某些结核分枝杆菌抗原的抗体反应通常也反映了潜伏感染，这解释了在结核病流行地区基于抗体的检测对活动性 TB 的检测性能不佳。我们的结果表明，针对选定的蛋白和非蛋白抗原以及不同的 Ig 类别的血清反应组合可能更适合用于 TB 血清学诊断。
