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

• Published in: PloS one Vol. 16; no. 12; p. e0261563
• Main Authors: Gojanovich, Greg S, Jacobson, Denise L, Broadwell, Carly, Karalius, Brad, Kirmse, Brian, Geffner, Mitchell E, Jao, Jennifer, Van Dyke, Russell B, McFarland, Elizabeth J, Silio, Margarita, Crain, Marilyn, Gerschenson, Mariana
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31-12-2021; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adolescent; AIDS; Analysis; Anti-Retroviral Agents - adverse effects; Anti-Retroviral Agents - therapeutic use; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Child; Child, Preschool; Children; Clinical trials; Confidence intervals; Cross-Sectional Studies; Cytokines - metabolism; Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast growth factors; Fibroblast Growth Factors - biosynthesis; Fibroblast Growth Factors - genetics; Follow-Up Studies; Genetic aspects; Growth Differentiation Factor 15 - biosynthesis; Growth Differentiation Factor 15 - genetics; Growth factors; Health aspects; HIV; HIV infection; HIV Infections - complications; HIV Infections - etiology; HIV Infections - metabolism; Human immunodeficiency virus; Humans; Infant; Infectious diseases; Male; Medicine and Health Sciences; Mitochondria; Mitochondria - metabolism; Mitochondrial Diseases - complications; Mitochondrial Diseases - diagnosis; Mitochondrial Diseases - metabolism; Mitochondrial DNA; Pediatrics; Regression Analysis; Risk; Statistical analysis; Young Adult; United States; New York; San Francisco California; United States > US; Massachusetts; Louisiana; Hawaii; Chicago Illinois; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0261563

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.