Delayed reconstitution of B cell immunity to pneumococcus in HIV-infected Malawian children on antiretroviral therapy
Delayed reconstitution of B cell immunity to pneumococcus in HIV-infected Malawian children on antiretroviral therapy
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DOI：
10.1016/j.jinf.2014.10.011
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发表时间：
2015-06-01
影响因子：
28.2
通讯作者：
Finn, Adam
中科院分区：
文献类型：
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作者：
Iwajomo, Oluwadamilola H.;Moons, Peter;Finn, Adam
目的：尽管抗逆转录病毒治疗（ART）可以恢复CD4（+）计数并抑制病毒载量，但艾滋病毒感染儿童发生包括侵袭性肺炎球菌病（IPD）在内的危及生命的感染的风险仍然增加。因此，我们研究了抗逆转录病毒治疗后对IPD的持续易感性是否与b细胞功能的不完全恢复有关。方法：对41名开始抗逆转录病毒治疗的艾滋病毒感染的马拉维儿童进行为期1年的随访，在第0、3、6和12个月采集血样，进行综合免疫分型和肺炎球菌特异性记忆b细胞酶联免疫点检测。此外，培养鼻咽拭子样本以确定肺炎球菌携带率。结果：ART治疗3个月后，CD4（+）百分比等主要淋巴细胞亚群明显恢复正常。12个月后，成熟幼稚B细胞(CD19(+) CD10(-) CD27（-) CD21(hi)）和静息记忆B细胞(CD19(+) CD27（+) CD21(hi)）的比例增加，易凋亡的成熟活化B细胞(CD19(+) CD21（lo) CD10(-)）的比例明显下降。然而，在高鼻咽部肺炎球菌携带率（83%）的情况下，肺炎球菌蛋白抗原特异性b细胞记忆的恢复更为延迟。结论：这些数据表明，在接受抗逆转录病毒治疗的慢性艾滋病毒感染儿童中，b细胞记忆谱和功能的改善比CD4(+) t细胞慢。这支持及早开始抗逆转录病毒治疗，并为研究肺炎球菌疫苗免疫的最佳时机提供信息。(C) 2014年作者。爱思唯尔有限公司代表英国感染协会出版。
Objective: Despite CD4(+) count restoration and viral load suppression with antiretroviral therapy (ART), HIV-infected children remain at increased risk of life-threatening infections including invasive pneumococcal disease (IPD). We therefore investigated whether persistent susceptibility to IPD following ART is associated with incomplete recovery of B-cell function.Methods: 41 HIV-infected Malawian children commencing ART were followed-up for a 1 year period during which time blood samples were collected at 0, 3, 6 and 12 months for comprehensive immunophenotyping and pneumomococcal-specific Memory B-cell Enzyme-Linked Immunospot assays. In addition, nasopharyngeal swab samples were cultured to determine pneumococcal carriage rates.Results: Normalization of major lymphocyte subsets such as CD4(+) percentages was evident following 3 months of ART. The proportions of mature naive B cells (CD19(+) CD10(-) CD27(-) CD21(hi)) and resting memory B cells (CD19(+) CD27(+) CD21(hi)) increased and apoptosis-prone mature activated B cells (CD19(+) CD21(lo) CD10(-)) decreased markedly by 12 months. However, in the context of high nasopharyngeal pneumococcal carriage rates (83%), restoration of pneumococcal protein antigen-specific B-cell memory was more delayed.Conclusions: These data show that, in chronically HIV-infected children receiving ART, improvement in B-cell memory profiles and function is slower than CD4(+) T-cells. This supports early initiation of ART and informs research into optimal timing of immunization with pneumococcal vaccines. (C) 2014 The Authors. Published by Elsevier Ltd on behalf of the The British Infection Association.