Van Epps Puja, Matining Roy M, Tassiopoulos Katherine, Anthony Donald D, Landay Alan, Kalayjian Robert C, Canaday David H
Geriatric Research Center Clinical Core (GRECC), Department of Infectious Diseases, Louis Stokes Cleveland VA Medical Center, Case Western Reserve University, Cleveland, Ohio, United States of America.
Harvard School of Public Health, Boston, Massachusetts, United States of America.
PLoS One. 2014 Sep 10;9(9):e107064. doi: 10.1371/journal.pone.0107064. eCollection 2014.
Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.
在一项针对开始抗逆转录病毒治疗(ART)的老年和年轻(≥45岁与≤30岁)HIV感染受试者的前瞻性年龄分层队列研究中,先前发现老年HIV感染受试者在初始抗逆转录病毒治疗期间有显著的B细胞扩增。在此,为了进一步描述这种扩增情况,我们使用同一队列中的一部分受试者,对老年和年轻HIV感染组在基线时以及ART治疗192周后的B细胞表型进行了特征分析,并将其与未感染的年龄匹配对照组进行比较。我们还研究了基线时的表型是否与12周时破伤风和甲型肝炎疫苗的反应相关。HIV感染组分析了46名受试者(21名老年,25名年轻),对照组分析了30名受试者(每个年龄组15名)。我们观察到,年轻受试者在ART治疗第192周后幼稚B细胞恢复正常,而老年受试者的幼稚B细胞增加到高于对照组的水平(p = 0.045)。与对照组相比,老年HIV感染组在基线时绝对静止记忆(RM)细胞计数显著更低,在ART治疗192周后数量恢复正常(p<0.001)。在合并的年轻和老年HIV感染受试者中,基线RM细胞计数与第12周破伤风疫苗抗体增加呈正相关(p = 0.01),但在对照组中无此相关性。年龄相关的幼稚B细胞扩增是一项新发现,我们讨论了对此观察结果的几种可能解释。基线时RM细胞与破伤风反应之间的关系可能有助于深入了解HIV感染对B细胞记忆功能和疫苗反应的影响。