宿主对结核分枝杆菌的免疫力与结核病风险：格陵兰人的一项纵向研究。
Host immunity to Mycobacterium tuberculosis and risk of tuberculosis: A longitudinal study among Greenlanders.
作者信息
Michelsen Sascha Wilk, Soborg Bolette, Agger Else Marie, Diaz Lars Jorge, Hoff Soren Tetens, Koch Anders, Sorensen Hans Christian Florian, Andersen Peter, Wohlfahrt Jan, Melbye Mads
机构信息
Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Department of Infectious Disease Immunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
出版信息
Vaccine. 2016 Nov 21;34(48):5975-5983. doi: 10.1016/j.vaccine.2016.09.047. Epub 2016 Oct 27.
BACKGROUND
Human immune responses to latent Mycobacterium tuberculosis (Mtb) infection (LTBI) may enable individuals to control Mtb infection and halt progression to tuberculosis (TB), a hypothesis applied in several novel TB vaccines. We aimed to evaluate whether immune responses to selected LTBI antigens were associated with subsequent reduced risk of progression to TB.
METHODS
We conducted a population-based cohort study in East Greenland (2012-2014) including individuals aged 5-31years. A personal identifier allowed follow-up in national registers including the TB notification register. Mtb infection was defined by a positive Quantiferon test. Immune responses to LTBI antigens were assessed by whole blood antigen stimulation and interferon gamma measurement.
RESULTS
Among 978 participants, 67 previously had TB. LTBI antigen (Rv1284, Rv2659, Rv2660c) immune response prevalence was 18%, 50%, 2% among Mtb-infected and 7%, 40%, 4% among non-infected (Quantiferon negative) participants. Among 911 participants without prior notified TB, 31 were notified with TB during study follow-up. Immune responses to LTBI antigens were not associated with reduced risk of subsequent TB; Rv1284 HR 0.92 (95%CI 0.28-3.04), Rv2659 HR 1.05 (95%CI 0.51-2.13), Rv2660c HR 3.06 (95%CI 0.70-13.37).
CONCLUSION
In this large population-based study, human immune responses to selected LTBI antigens were not found to be strongly associated with reduced risk of subsequent TB.
背景
人类对潜伏性结核分枝杆菌（Mtb）感染（LTBI）的免疫反应可能使个体能够控制Mtb感染并阻止其发展为结核病（TB），这一假设已应用于多种新型TB疫苗。我们旨在评估对选定LTBI抗原的免疫反应是否与随后降低的TB发病风险相关。
方法
我们在东格陵兰岛（2012 - 2014年）开展了一项基于人群的队列研究，纳入年龄在5 - 31岁的个体。通过个人标识符在包括TB通报登记册在内的国家登记处进行随访。Mtb感染通过结核菌素试验阳性来定义。通过全血抗原刺激和干扰素γ测量来评估对LTBI抗原的免疫反应。
结果
在978名参与者中，67人曾患TB。在Mtb感染的参与者中，LTBI抗原（Rv1284、Rv2659、Rv2660c）免疫反应的患病率分别为18%、50%、2%；在未感染（结核菌素试验阴性）参与者中分别为7%、40%、4%。在911名既往未通报患TB的参与者中，31人在研究随访期间被通报患TB。对LTBI抗原的免疫反应与随后降低的TB发病风险无关；Rv1284风险比为0.92（95%置信区间0.28 - 3.04），Rv2659风险比为1.05（95%置信区间0.5–2.13），Rv2660c风险比为3.06（95%置信区间0.70 - 13.37）。
结论
在这项基于人群的大型研究中，未发现人类对选定LTBI抗原的免疫反应与随后降低的TB发病风险有强烈关联。
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