Pro-inflammatory and anti-inflammatory immune biomarkers as predictors of neurodevelopment in young children exposed to HIV.

IF 3.4 2区 医学 Q3 IMMUNOLOGY
AIDS Pub Date : 2025-07-01 Epub Date: 2025-02-18 DOI:10.1097/QAD.0000000000004162
Wei Li, Ashley Egler, Eren Oyungu, Ziyi Yang, Huiping Xu, Jeong Hoon Jang, Megan S McHenry, Qigui Yu, Alka Khaitan
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Abstract

Objective: Higher inflammation and lower neurodevelopmental outcomes have been reported in children exposed to HIV but uninfected (CHEU) compared to children unexposed to HIV (CHU) during infancy, but whether these differences persist in early childhood is unclear. We assessed pro-inflammatory and anti-inflammatory biomarkers and their associations with neurodevelopmental outcomes in CHEU and CHU aged 18-36 months.

Design: Cross-sectional study of 45 CHEU and 36 CHU aged 18-36 months enrolled in Eldoret, Kenya.

Methods: Plasma levels of 65 cytokines, chemokines, growth factors, and soluble receptors, and 16 soluble immune checkpoints (ICPs) were quantified using multiplex immunoassays. Monocyte activation (sCD14, sCD163) and endothelial activation (CD146, ICAM-1, VCAM-1) plasma levels were measured by ELISAs. Neurodevelopmental outcomes were assessed using the culturally adapted developmental assessment of cognition, language, and motor function. Predictors of neurodevelopmental outcomes were assessed using Bayesian Model Averaging of the linear regression model.

Results: CHEU exhibited lower levels of several chemokine and growth factors and four inflammatory cytokines compared to CHU: A proliferation inducing ligand (APRIL) ( P  = 0.03), IL-12p70 ( P  < 0.001), macrophage migration inhibitory factor (MIF) ( P  = 0.002), and Tweak ( P  = 0.003). Conversely, two soluble ICPs, CD40 ( P  = 0.02) and TIM3 ( P  = 0.001), were higher in CHEU compared to CHU. IL-22 and SDF-1α emerged as the strongest predictors of neurodevelopment in CHEU and CHU, respectively.

Conclusion: In early childhood, CHEU exhibited an immunosuppressive rather than inflammatory biomarker profile. Immune biomarkers more frequently predicted neurodevelopmental outcomes than social and demographic factors, and the predictors of cognitive, motor, and language outcomes differed between CHU and CHEU. Further research is necessary to explore the connection between childhood neurodevelopment and immune biomarkers.

亲和抗炎免疫生物标志物作为暴露于HIV的幼儿神经发育的预测因子。
目的:据报道,在婴儿期暴露于HIV但未感染(CHEU)的儿童与未暴露于HIV (CHU)的儿童相比,有更高的炎症和更低的神经发育结局(ND),但这些差异是否在幼儿期持续尚不清楚。我们评估了18-36月龄CHEU和CHU的促炎和抗炎生物标志物及其与ND的关系。设计:横断面研究,在肯尼亚埃尔多雷特登记的年龄18-36个月的45名CHEU和36名CHU。方法:采用多重免疫分析法定量测定65种细胞因子、趋化因子、生长因子、可溶性受体和16种可溶性免疫检查点(icp)的血浆水平。elisa法检测血浆单核细胞活化(sCD14、sCD163)和内皮细胞活化(CD146、ICAM-1、VCAM-1)水平。使用认知、语言和运动功能的文化适应性发展评估来评估ND。采用线性回归模型的贝叶斯平均模型评估ND的预测因子。结果:与CHU相比,CHEU表现出较低的几种趋化因子和生长因子以及四种炎症因子水平:APRIL (p = 0.03), IL-12p70 (p)。结论:在儿童早期,CHEU表现出免疫抑制而非炎症生物标志物特征。免疫生物标志物比社会和人口因素更能预测ND,而认知、运动和语言结果的预测指标在CHU和CHEU之间存在差异。需要进一步研究儿童神经发育与免疫生物标志物之间的联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
AIDS
AIDS 医学-病毒学
CiteScore
5.90
自引率
5.30%
发文量
478
审稿时长
3 months
期刊介绍: ​​​​​​​​​​​​​​​​​Publishing the very latest ground breaking research on HIV and AIDS. Read by all the top clinicians and researchers, AIDS has the highest impact of all AIDS-related journals. With 18 issues per year, AIDS guarantees the authoritative presentation of significant advances. The Editors, themselves noted international experts who know the demands of your work, are committed to making AIDS the most distinguished and innovative journal in the field. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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