From the Department of Pediatrics, University of Washington, Seattle, Washington.
Department of Medicine, University of Washington, Seattle, Washington.
Pediatr Infect Dis J. 2021 Oct 1;40(10):922-929. doi: 10.1097/INF.0000000000003254.
HIV-exposed uninfected (HEU) infants have increased risk of tuberculosis (TB). Testing for Mycobacterium tuberculosis (Mtb) infection is limited by reduced Quantiferon (QFT) sensitivity in infants and tuberculin skin test (TST) cross-reactivity with Bacillus Calmette-Guérin vaccine. Our objective is to assess if non-IFNγ cytokine responses to Mtb-specific antigens have improved sensitivity in detecting Mtb infection in HEU infants compared with QFT.
HEU infants were enrolled in a randomized clinical trial of isoniazid preventive therapy (IPT) to prevent Mtb infection in Kenya (N = 300) and assessed at 12 months postrandomization (14 months of age) by TST and QFT-Plus. Non-IFNγ cytokine secretion (IL2, TNF, IP10, N = 229) in QFT-Plus supernatants was measured using Luminex assay. Logistic regression was used to assess the effect of IPT on Mtb infection outcomes in HEU infants.
Three of 251 (1.2%) infants were QFT-Plus positive. Non-IFNγ Mtb antigen-specific responses were detected in 12 additional infants (12/229, 5.2%), all TST negative. IPT was not associated with Mtb infection defined as any Mtb antigen-specific cytokine response (odds ratio = 0.7, P = 0.54). Mtb antigen-specific IL2/IP10 responses had fair correlation (τ = 0.25). Otherwise, non-IFNγ cytokine responses had minimal correlation with QFT-Plus and no correlation with TST size.
We detected non-IFNg Mtb antigen-specific T-cell responses in 14-month HEU infants. Non-IFNg cytokines may be more sensitive than IFNg in detecting infant Mtb infection. IPT during the first year of life was not associated with Mtb infection measured by IFNg, IL2, IP10 and TNF Mtb-specific responses.
艾滋病毒暴露未感染（HEU）婴儿患结核病（TB）的风险增加。由于婴儿中 Quantiferon（QFT）的敏感性降低以及结核菌素皮肤试验（TST）与卡介苗疫苗的交叉反应，对结核分枝杆菌（Mtb）感染的检测受到限制。我们的目的是评估与 QFT 相比，针对 Mtb 特异性抗原的非 IFNγ细胞因子反应是否可提高检测 HEU 婴儿 Mtb 感染的敏感性。
在肯尼亚，我们将 HEU 婴儿纳入一项异烟肼预防治疗（IPT）的随机临床试验中，以预防 Mtb 感染（N=300），并在随机分组后 12 个月（14 个月龄）通过 TST 和 QFT-Plus 进行评估。使用 Luminex 测定法测量 QFT-Plus 上清液中非 IFNγ细胞因子（IL2、TNF、IP10、N=229）的分泌。Logistic 回归用于评估 IPT 对 HEU 婴儿 Mtb 感染结局的影响。
251 名婴儿中有 3 名（1.2%）QFT-Plus 阳性。在另外 12 名婴儿（12/229，5.2%）中检测到非 IFNγ Mtb 抗原特异性反应，所有 TST 均为阴性。IPT 与任何 Mtb 抗原特异性细胞因子反应定义的 Mtb 感染无关（比值比=0.7，P=0.54）。Mtb 抗原特异性 IL2/IP10 反应具有适度相关性（τ=0.25）。否则，非 IFNγ细胞因子反应与 QFT-Plus 相关性最小，与 TST 大小无相关性。
我们在 14 个月大的 HEU 婴儿中检测到非 IFNγ Mtb 抗原特异性 T 细胞反应。非 IFNγ细胞因子可能比 IFNγ更敏感，可检测婴儿 Mtb 感染。在生命的第一年进行 IPT 与通过 IFNγ、IL2、IP10 和 TNF 特异性 Mtb 反应测量的 Mtb 感染无关。
