Reid Duncan, Shenoi Sheela, Singh Ravesh, Wang Max, Patel Vinod, Das Rituparna, Hiramen Keshni, Moosa Yunus, Eksteen Francois, Moll Anthony P, Ndung'u Thumbi, Kasprowicz Victoria, Leng Lin, Friedland Gerald H, Bucala Richard
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Cytokine X. 2019 Feb 16;1(1):100004. doi: 10.1016/j.cytox.2019.100004. eCollection 2019 Mar.
Host immunity is crucial for controlling infection. Functional polymorphisms in the cytokine macrophage migration inhibitory factor (MIF) show global population stratification, with the highest prevalence of low expression alleles found in sub-Saharan Africans, which is a population with the greatest confluence of both TB and HIV infection and disease. We investigated the association between alleles and tuberculosis (TB) and HIV in South Africa. We acquired clinical information and determined the frequency of two promoter variants: a functional -794 CATT microsatellite and an associated -173 G/C SNP in two HIV-positive cohorts of patients with active laboratory-confirmed TB and in controls without active TB who were all HIV positive. We found a greater frequency of low expression promoter variants (-794 CATT) among TB disease cases compared to controls (OR = 2.03, p = 0.023), supporting a contribution of genetic low expression to the high prevalence of TB in South Africa. Among those with HIV, circulating MIF levels also were associated with lower CD4 cell counts irrespective of TB status (p = 0.016), suggesting an influence of HIV immunosuppression on expression.
宿主免疫对于控制感染至关重要。细胞因子巨噬细胞移动抑制因子（MIF）的功能多态性呈现全球人群分层现象，低表达等位基因在撒哈拉以南非洲人中的流行率最高，而该人群是结核病和艾滋病毒感染及疾病合并最为严重的群体。我们在南非调查了这些等位基因与结核病（TB）和艾滋病毒之间的关联。我们获取了临床信息，并确定了两个启动子变体的频率：一个功能性的-794 CATT微卫星以及一个相关的-173 G/C单核苷酸多态性，研究对象为两个实验室确诊为活动性结核病的艾滋病毒阳性患者队列以及均为艾滋病毒阳性但无活动性结核病的对照组。我们发现，与对照组相比，结核病患者中低表达启动子变体（-794 CATT）的频率更高（比值比=2.03，p=0.023），这支持了基因低表达对南非结核病高流行率的影响。在艾滋病毒感染者中，无论结核病状态如何，循环MIF水平也与较低的CD4细胞计数相关（p=0.016），这表明艾滋病毒免疫抑制对MIF表达有影响。
