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
Year: 2021
Type: article
Abstract: BACKGROUND: 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). SETTING: Cross-sectional study of CPHIV from Pediatric ACTG 219/219C classified by Mitochondrial Disease Criteria (MDC) that defines scores 2-4 as "possible" MD. METHODS: 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. RESULTS: 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. CONCLUSION: FGF21 and GDF15 levels may be useful biomarkers to screen for CPHIV with mitochondrial dysfunction.
Source: PLoS ONE
Authors: 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, for the Pediatric HIV/AIDS Cohort Study
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,749
Funders: U.S. Department of Health and Human Services, Pfizer, Vanderbilt University, University of Miami, Wayne State University, Emory University, Bunning Food Allergy Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, State University of New York, Tulane University, University of Cincinnati, Harvard T.H. Chan School of Public Health, University of Hawai'i, University of South Carolina, University of South Florida, University of South Alabama, Baystate Health, Vanderbilt University Medical Center, Millendo Therapeutics, Connecticut Children's Medical Center, Novo Nordisk, National Institutes of Health, Leonard M. Miller School of Medicine, SUNY Downstate Medical Center, State University of New York Upstate Medical University, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development, David Geffen School of Medicine, University of California, Los Angeles, Daiichi Sankyo Europe
OpenAlex ID: W4206485655