A new diagnostic indication device of a biomarker growth differentiation factor 15 for mitochondrial diseases: From laboratory to automated inspection

Figures

• 

  FIGURE 1. STARD flow diagram of patients with mitochondrial diseases, disease controls, and healthy controls. A, Forty‐eight patients with mitochondrial diseases, who met the clinicopathologic diagnostic criteria, were enrolled between 2017 and 2020. B, One hundred and sixteen disease controls who had nonmitochondrial diseases, 89, 4, 9, and 9 of whom had neurodegenerative diseases, DM, HF, and RF, respectively. C, Ninety‐one healthy controls were recruited, 86 of whom underwent the reference test. DM, diabetes mellitus; HF, heart failure; KSS, Kearns‐Sayre syndrome; LS, Leigh syndrome; MELA, mitochondrial encephalopathy and lactic acidosis; MELAS, mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes; and RF, renal failure

• 

  FIGURE 2. The box‐and‐whisker plots of serum GDF15 concentrations measured with the LTIA device in analyzed individuals. Patients with mitochondrial diseases included patients with MELAS, MELA, LS, or KSS, a patient with genetically unclassified MD, as well as asymptomatic individuals. Disease controls included patients with neurodegenerative disorders, DM, HF, or RF. HF, heart failure; KSS, Kearns‐Sayre syndrome; LS, Leigh syndrome; LTIA, latex‐enhanced turbidimetric immunoassay; MELA, mitochondrial encephalopathy and lactic acidosis; MELAS, mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes; RF: renal failure. The horizontal bold line, the box length, and the dotted line represent the median, the interquartile range, and the whiskers, respectively. The least and greatest values, as well as the outliers are also expressed. LTIA, latex‐enhanced turbidimetric immunoassay

• 

  FIGURE 3. ROC analyses of serum GDF15 concentrations measured with the ELISA kit and the LTIA device in patients with MDs versus neurodegenerative controls and healthy controls. A, ROC curve of serum GDF15 concentrations measured with the ELISA kit. B, ROC curve of serum GDF15 concentrations measured with the LTIA device. C, Correlation of GDF15 concentrations between ELISA kit and the LTIA device. The solid line and dotted line in (A) and (B) show the ROC curve based on 35 patients with MDs versus neurodegenerative disorders and 35 patients with MDs versus healthy controls, respectively. Circles and crosses on (A) and (B) indicate points corresponding to cutoffs of Youden index based on the analysis of patients with MDs versus neurodegenerative controls and patients with MDs versus healthy controls, respectively. Youden index for patients with MDs versus neurodegenerative controls and patients with MDs versus healthy controls were 927.0 pg/mL and 476.0 pg/mL by ELISA, and 689.5 U/mL and 693.5 U/mL by LTIA, respectively. The solid line in (C) represents the correlation cure, and the dotted lines the 95% confidence interval. ELISA, enzyme‐linked immunosorbent assay; MD, mitochondrial…