Abebe Fekadu, Belay Mulugeta, Legesse Mengistu, K L M C Franken, Ottenhoff Tom H M
University of Oslo, Faculty of Medicine, Institute of Health and Society, Department of Community Medicine and Global health, Oslo, Norway.
Center for Immuno-biology, Bart's and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
PLoS One. 2018 Jan 26;13(1):e0190989. doi: 10.1371/journal.pone.0190989. eCollection 2018.
As part of a major project to investigate protective and diagnostic immune markers against tuberculosis (TB), we measured antibody isotype responses to Mycobacterium tuberculosis (Mtb) antigens (LAM, Rv2031, and HBHA) in cohorts of 149 pulmonary tuberculosis patients (PTBP), 148 household contacts (HHCs), and 68 community controls (CCs) in an endemic setting. ELISA was used to measure levels of IgA, IgG, and IgM from sera of cohorts at baseline, and at 6 and 12 months from entry. The results show that there were significant differences in IgA, IgG, and IgM responses to the different antigens and in the three cohorts. At baseline, the level of IgM against RV2031 and LAM did not vary between cohorts, but the levels of IgA and IgG against Rv2031 were significantly higher in PTB patients than HHCs and CCs, followed by HHCs, and the lowest in CCs. In patients, there was a significant variation in antibody responses before and after chemotherapy. The levels of IgA and IgG against HBHA, and IgA against Rv2031 decreased significantly and remained low, while IgA and IgG against LAM increased significantly and remained high following chemotherapy. However, the levels of IgM against Rv2031 and LAM increased at 6 months but decreased again at 12 months. IgM against HBHA did not show any significant variation before and after chemotherapy. Similarly, there were also significant variations in antibody responses in HHCs over time. Our results show that there are significant variations in IgA, IgG and IgM responses to the different antigens and in the three cohorts, implying that not all antibody isotype responses are markers of clinical TB. In addition, the current and previous studies consistently show that IgA and IgG against Rv2031 discriminate between clinical disease, Mtb-infected and non-infected individuals.
作为一项调查结核病(TB)保护性和诊断性免疫标志物的重大项目的一部分,我们在地方病流行环境中,对149例肺结核患者(PTBP)、148例家庭接触者(HHC)和68例社区对照者(CC)队列,测量了针对结核分枝杆菌(Mtb)抗原(脂阿拉伯甘露聚糖、Rv2031和肝素结合血凝素)的抗体亚型反应。采用酶联免疫吸附测定法(ELISA)测量各队列血清在基线时、入组后6个月和12个月时的IgA、IgG和IgM水平。结果显示,不同抗原以及三个队列的IgA、IgG和IgM反应存在显著差异。在基线时,各队列中针对RV2031和脂阿拉伯甘露聚糖的IgM水平无差异,但肺结核患者中针对Rv2031的IgA和IgG水平显著高于家庭接触者和社区对照者,其次是家庭接触者,社区对照者最低。在患者中,化疗前后抗体反应存在显著差异。化疗后,针对肝素结合血凝素的IgA和IgG水平以及针对Rv2031的IgA水平显著下降并维持在低水平,而针对脂阿拉伯甘露聚糖的IgA和IgG水平显著升高并维持在高水平。然而,针对Rv2031和脂阿拉伯甘露聚糖的IgM水平在6个月时升高,但在12个月时再次下降。针对肝素结合血凝素的IgM在化疗前后未显示任何显著变化。同样,家庭接触者的抗体反应随时间也有显著变化。我们的结果表明,不同抗原以及三个队列的IgA、IgG和IgM反应存在显著差异,这意味着并非所有抗体亚型反应都是临床结核病的标志物。此外,当前和既往研究一致表明,针对Rv2031的IgA和IgG可区分临床疾病、感染Mtb的个体和未感染个体。