Payne Helen, Chain Gabriel, Adams Stuart, Hunter Patricia, Luckhurst Natasha, Gilmour Kimberly, Lewis Joanna, Babiker Abdel, Cotton Mark, Violari Avy, Gibb Diana, Callard Robin, Klein Nigel
1 UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
2 Clinical Trials Unit, Medical Research Council, London, United Kingdom.
AIDS Res Hum Retroviruses. 2019 Jan;35(1):33-39. doi: 10.1089/AID.2018.0170. Epub 2018 Dec 26.
In this study, we aimed to quantify KREC (kappa-deleting recombination excision circle) levels and naive B cell output in healthy HIV-uninfected children, compared with HIV-infected South African children, before and after starting ART (antiretroviral therapy). Samples were acquired from a Child Wellness Clinic (n = 288 HIV-uninfected South African children, 2 weeks-12 years) and the Children with HIV Early Antiretroviral Therapy (CHER) trial (n = 153 HIV-infected South African children, 7 weeks-8 years). Naive B cell output was estimated using a mathematical model combining KREC levels to reflect B cell emigration into the circulation, flow cytometry measures of naive unswitched B cells to quantify total body naive B cells, and their rates of proliferation using the intracellular marker Ki67. Naive B cell output increases from birth to 1 year, followed by a decline and plateau into late childhood. HIV-infected children on or off ART had higher naive B cell outputs than their uninfected counterparts (p = .01 and p = .04). This is the first study to present reference ranges for measurements of KRECs and naive B cell output in healthy and HIV-infected children. Comparison between HIV-uninfected healthy children and HIV-infected children suggests that HIV may increase naive B cell output. Further work is required to fully understand the mechanisms involved and clinical value of measuring naive B cell output in children.
在本研究中，我们旨在对未感染艾滋病毒的健康儿童的κ-缺失重组切除环（KREC）水平和初始B细胞输出量进行量化，并与感染艾滋病毒的南非儿童在开始抗逆转录病毒治疗（ART）前后进行比较。样本取自一家儿童健康诊所（n = 288名未感染艾滋病毒的南非儿童，年龄在2周-12岁之间）以及艾滋病毒感染儿童早期抗逆转录病毒治疗（CHER）试验（n = 153名感染艾滋病毒的南非儿童，年龄在7周-8岁之间）。使用一个数学模型来估计初始B细胞输出量，该模型结合KREC水平以反映B细胞向循环系统的迁移、通过流式细胞术检测初始未转换B细胞来量化全身初始B细胞，并使用细胞内标志物Ki67来检测其增殖速率。初始B细胞输出量从出生到1岁增加，随后下降并在儿童晚期趋于平稳。接受或未接受ART治疗的感染艾滋病毒儿童的初始B细胞输出量高于未感染儿童（p = 0.01和p = 0.04）。这是第一项给出健康儿童和感染艾滋病毒儿童KREC测量值及初始B细胞输出量参考范围的研究。未感染艾滋病毒的健康儿童与感染艾滋病毒儿童之间的比较表明，艾滋病毒可能会增加初始B细胞输出量。需要进一步开展工作以充分了解其中涉及的机制以及测量儿童初始B细胞输出量的临床价值。
