Yu Chunjiang, Seaton Melanie, Letendre Scott, Heaton Robert, Al-Harthi Lena
aDepartment of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois bDepartment of Medicine cDepartment of Psychiatry University of California, San Diego, California, USA.
AIDS. 2017 Jun 19;31(10):1379-1385. doi: 10.1097/QAD.0000000000001481.
Dickkopf-related protein 1 (DKK1) is a soluble antagonist of the Wningless (Wnt) pathway. It binds to and sequesters low-density lipoprotein receptor-related proteins 5/6 away from Wnts. Because the Wnt pathway regulates synaptic transmission and plasticity, we hypothesized that increased DKK1 would increase the risk for neurocognitive impairment (NCI) in HIV-positive (HIV) individuals. We evaluated, here, the relationship between plasma DKK1 and global NCI.
Plasma samples and data from 41 HIV to 42 HIV adults were obtained from the University of California, San Diego, California, USA. Concentrations of DKK1 and a comparator protein, monocyte chemoattractant protein-1 (MCP-1), were quantified in plasma by immunoassay. All study participants completed a standardized comprehensive neuropsychological test battery and their performance was summarized using the global deficit score method.
A higher DKK1 level was associated with NCI among HIV participants (d = 0.63, P = 0.05), particularly among the 26 participants whose plasma HIV RNA level was suppressed (d = 0.74, P = 0.08). DKK1 level was not associated with NCI among HIV participants (P = 0.98). was not associated with NCI in either group. In HIV adults with suppressed plasma HIV RNA, a receiver operator characteristic curve identified that a DKK1 level of at least 735 pg/ml had a positive predictive value of 83.3% for a diagnosis of NCI. This association did not weaken after accounting for the effect of AIDS, nadir CD4 T-cell count, addictive drug use, or demographic characteristics.
DKK1 is a specific biomarker for NCI in HIV adults, implicating the Wnt pathway in HIV neuropathogenesis.
Dickkopf相关蛋白1（DKK1）是Wnt信号通路的可溶性拮抗剂。它与低密度脂蛋白受体相关蛋白5/6结合并使其与Wnt分离。由于Wnt信号通路调节突触传递和可塑性，我们推测DKK1水平升高会增加HIV阳性个体发生神经认知障碍（NCI）的风险。在此，我们评估了血浆DKK1与整体NCI之间的关系。
血浆样本和41至42名HIV成年患者的数据来自美国加利福尼亚州圣地亚哥的加利福尼亚大学。通过免疫测定法定量血浆中DKK1和一种对照蛋白单核细胞趋化蛋白-1（MCP-1）的浓度。所有研究参与者均完成了标准化的综合神经心理测试组，并使用整体缺陷评分法总结其表现。
在HIV参与者中，较高的DKK1水平与NCI相关（d = 0.63，P = 0.05），特别是在血浆HIV RNA水平被抑制的26名参与者中（d = 0.74，P = 0.08）。在HIV参与者中，DKK1水平与NCI无关（P = 0.98）。在两组中均与NCI无关。在血浆HIV RNA被抑制的HIV成年患者中，受试者工作特征曲线确定，DKK1水平至少为735 pg/ml时，对NCI诊断的阳性预测值为83.3%。在考虑艾滋病、最低CD4 T细胞计数、成瘾药物使用或人口统计学特征的影响后，这种关联并未减弱。
DKK1是HIV成年患者NCI的特异性生物标志物，提示Wnt信号通路参与HIV神经发病机制。
