Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders



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Peñas, Ana and Fernández de la Torre, Miguel and Laine Menéndez, Sara and Lora Pablos, David and Illescas, María and García Bartolomé, Alberto and Morales Conejo, Montserrat and Arenas, Joaquín and Martín Casanueva, Miguel Ángel and Morán Calvo-Sotelo, María Luz and Domínguez González, Cristina and Ugalde, Cristina (2021) Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders. International Journal of Molecular Sciences, 22 (12). p. 6396. ISSN 1422-0067

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Mitochondrial disorders (MD) comprise a group of heterogeneous clinical disorders for which non-invasive diagnosis remains a challenge. Two protein biomarkers have so far emerged for MD detection, FGF-21 and GDF-15, but the identification of additional biomarkers capable of improving their diagnostic accuracy is highly relevant. Previous studies identified Gelsolin as a regulator of cell survival adaptations triggered by mitochondrial defects. Gelsolin presents a circulating plasma isoform (pGSN), whose altered levels could be a hallmark of mitochondrial dysfunction. Therefore, we investigated the diagnostic performance of pGSN for MD relative to FGF-21 and GDF-15. Using ELISA assays, we quantified plasma levels of pGSN, FGF-21, and GDF-15 in three age- and gender-matched adult cohorts: 60 genetically diagnosed MD patients, 56 healthy donors, and 41 patients with unrelated neuromuscular pathologies (non-MD). Clinical variables and biomarkers’ plasma levels were compared between groups. Discrimination ability was calculated using the area under the ROC curve (AUC). Optimal cut-offs and the following diagnostic parameters were determined: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and efficiency. Comprehensive statistical analyses revealed significant discrimination ability for the three biomarkers to classify between MD and healthy individuals, with the best diagnostic performance for the GDF-15/pGSN combination. pGSN and GDF-15 preferentially discriminated between MD and non-MD patients under 50 years, whereas FGF-21 best classified older subjects. Conclusion: pGSN improves the diagnosis accuracy for MD provided by FGF-21 and GDF-15.

Item Type:Article
Uncontrolled Keywords:mitochondrial disorders; OXPHOS deficiency; biomarkers; plasma GSN; FGF-21; GDF-15
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Endocrinology
Medical sciences > Medicine > Medical genetics
ID Code:71244
Deposited On:15 Mar 2022 14:10
Last Modified:16 Mar 2022 12:45

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