PLoS ONE (Jan 2021)

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.

  • Greg S Gojanovich,
  • Denise L Jacobson,
  • Carly Broadwell,
  • Brad Karalius,
  • Brian Kirmse,
  • Mitchell E Geffner,
  • Jennifer Jao,
  • Russell B Van Dyke,
  • Elizabeth J McFarland,
  • Margarita Silio,
  • Marilyn Crain,
  • Mariana Gerschenson,
  • Pediatric HIV/AIDS Cohort Study

DOI
https://doi.org/10.1371/journal.pone.0261563
Journal volume & issue
Vol. 16, no. 12
p. e0261563

Abstract

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BackgroundIn 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).SettingCross-sectional study of CPHIV from Pediatric ACTG 219/219C classified by Mitochondrial Disease Criteria (MDC) that defines scores 2-4 as "possible" MD.MethodsEach 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.ResultsMedian 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 pConclusionFGF21 and GDF15 levels may be useful biomarkers to screen for CPHIV with mitochondrial dysfunction.