University of Hawaii at Manoa, Honolulu, Hawaii, United States of America.
Harvard TH Chan School of Public Health, Boston, Massachusetts, United States of America.
PLoS One. 2021 Dec 31;16(12):e0261563. doi: 10.1371/journal.pone.0261563. eCollection 2021.
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.
在感染 HIV 的人群中，由于临床症状不具有特异性且模式不一致，因此很难诊断线粒体疾病（MD）。成纤维细胞生长因子 21（FGF21）和生长分化因子 15（GDF15）是无 HIV 感染的 MD 患者中升高的线粒体细胞因子，与 HIV 感染者的心血管代谢合并症相关。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 之间的关系。
根据线粒体疾病标准（MDC）将 CPHIV 进行分类的儿科 AIDS 临床试验组 219/219C 的横断面研究，MDC 得分为 2-4 为“可能”MD。
每个 MDC 等于 4（MDC4；n=23）的病例均与一个基于日历日期随机选择的无 MDC（MDC0；n=23）的对照病例相匹配。还评估了 MDC 等于 3（MDC3；n=71）的未匹配病例。通过 ELISA 检测血浆样本。使用 Wilcoxon 检验比较线粒体细胞因子分布，计算 Spearman 相关系数，并通过条件逻辑回归评估与 MD 状态的关联。
MDC4（143.9 和 1441.1 pg/mL）、MDC3（104.0 和 726.5 pg/mL）的 FGF21 和 GDF15 浓度中位数分别最高，而对照组（89.4 和 484.7 pg/mL）最低。在 MDC4 与 MDC0 之间，FGF21（配对 Wilcoxon 秩和检验 p=0.002）和 GDF15（配对 Wilcoxon 秩和检验 p<0.001）的分布不同。所有参与者的线粒体细胞因子浓度均相关（r=0.33；p<0.001）。未调整的 MDC4 与 MDC0 比值比为 5.2（95%置信区间（CI）：1.06-25.92），FGF21 为 3.5（95%CI：1.19-10.25）。在调整协变量后，这些关系仍然存在。
FGF21 和 GDF15 水平可能是筛查 CPHIV 线粒体功能障碍的有用生物标志物。
