Associations of FGF21 and GDF15 with mitochondrial dysfunction in children living with perinatally-acquired HIV: A cross-sectional evaluation of pediatric AIDS clinical trials group 219/219C.
Associations of FGF21 and GDF15 with mitochondrial dysfunction in children living with perinatally-acquired HIV: A cross-sectional evaluation of pediatric AIDS clinical trials group 219/219C.
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DOI：
10.1371/journal.pone.0261563
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Pediatric HIV/AIDS Cohort Study
中科院分区：
文献类型：
--
作者：
Gojanovich GS;Jacobson DL;Broadwell C;Karalius B;Kirmse B;Geffner ME;Jao J;Van Dyke RB;McFarland EJ;Silio M;Crain M;Gerschenson M;Pediatric HIV/AIDS Cohort Study
在艾滋病毒感染者中，线粒体疾病（MD）很难诊断，因为临床症状是非特异性的，模式不一致。成纤维细胞生长因子21（FGF 21）和生长分化因子15（GDF 15）是在无HIV的MD患者中升高的丝裂因子，并与HIV感染成人的心脏代谢合并症相关。我们评估了这些生物标志物与围产期获得性HIV感染（CPHIV）儿童MD的关系。根据线粒体疾病标准（MDC）分类的儿科ACTG 219/219 C的CPHIV横断面研究，将评分2-4定义为“可能”MD。根据日历日期，将MDC等于4（MDC 4; n = 23）的每个病例与一个随机选择的未显示MDC（MDC 0; n = 23）的对照组进行匹配。还评估了MDC等于3（MDC 3; n = 71）的不匹配病例。通过ELISA测定接近诊断的血浆样品。使用Wilcoxon检验比较线粒体因子分布，计算斯皮尔曼相关性，并通过条件Logistic回归评估与MD状态的关联。中值FGF 21和GDF 15浓度分别在MDC 4中最高（143.9和1441.1 pg/mL），然后是MDC 3（104.0和726.5 pg/mL），并且在对照中最低（89.4和484.7 pg/mL）。FGF 21（配对Wilcoxon秩和p = 0.002）和GDF 15（配对Wilcoxon秩和p<0.001）的分布在MDC 4与MDC 0中不同。所有参与者的丝裂素浓度均相关（r = 0.33; p<0.001）。未校正的MDC 4与MDC 0的比值比为FGF 21为5.2 [95%置信区间（CI）：1.06-25.92]，GDF 15为3.5（95%CI：1.19-10.25）。协变量调整后，相关性持续存在。FGF 21和GDF 15水平可能是有用的生物标志物，以筛选CPHIV与线粒体功能障碍。
In persons living with HIV, mitochondrial disease (MD) is difficult to diagnose, as clinical signs are non-specific with inconsistent patterns. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are mitokines elevated in MD patients without HIV, and associated with cardiometabolic comorbidities in adults living with HIV. We assessed relationships of these biomarkers with MD in children living with perinatally-acquired HIV infection (CPHIV). Cross-sectional study of CPHIV from Pediatric ACTG 219/219C classified by Mitochondrial Disease Criteria (MDC) that defines scores 2–4 as “possible” MD. Each case with MDC equaling 4 (MDC4; n = 23) was matched to one randomly selected control displaying no MDC (MDC0; n = 23) based on calendar date. Unmatched cases with MDC equaling 3 (MDC3; n = 71) were also assessed. Plasma samples proximal to diagnoses were assayed by ELISA. Mitokine distributions were compared using Wilcoxon tests, Spearman correlations were calculated, and associations with MD status were assessed by conditional logistic regression. Median FGF21 and GDF15 concentrations, respectively, were highest in MDC4 (143.9 and 1441.1 pg/mL), then MDC3 (104.0 and 726.5 pg/mL), and lowest in controls (89.4 and 484.7 pg/mL). Distributions of FGF21 (paired Wilcoxon rank sum p = 0.002) and GDF15 (paired Wilcoxon rank sum p<0.001) differed in MDC4 vs MDC0. Mitokine concentrations were correlated across all participants (r = 0.33; p<0.001). Unadjusted odds ratios of being MDC4 vs MDC0 were 5.2 [95% confidence interval (CI): 1.06–25.92] for FGF21 and 3.5 (95%CI: 1.19–10.25) for GDF15. Relationships persisted after covariate adjustments. FGF21 and GDF15 levels may be useful biomarkers to screen for CPHIV with mitochondrial dysfunction.