Delayed reconstitution of B cell immunity to pneumococcus in HIV-infected Malawian children on antiretroviral therapy

作者：Iwajomo Oluwadamilola H; Moons Peter; Nkhata Rose; Mzinza David; Ogunniyi Abiodun D; Williams Neil A; Heyderman Robert S; Finn Adam^*

来源：Journal of Infection, 2015, 70(6): 616-623.

DOI：10.1016/j.jinf.2014.10.011

• HIV
• Antiretroviral therapy
• Children
• Malawi
• Pneumococcal infection
• Memory B cells
• ELISPOT

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.

• 出版日期2015-6