The mitochondrial disease biomarker GDF15 is dynamic, quantifiable in saliva, and correlates with disease severity.
Level 4 - case-series / case-control
Observational case-control and physiological challenge study comparing 40 mitochondrial disease patients to healthy controls.
PubMed 40602037 · doi:10.1016/j.ymgme.2025.109179
What was done
Analyzed GDF15 levels across 290 plasma and 860 saliva aliquots from 40 patients with primary mitochondrial disease (25 with m.3243 A > G mutation, 15 with single large-scale mtDNA deletions) and healthy controls. Tissue expression of GDF15 was profiled across 48 tissues using the GTEx dataset. Researchers measured GDF15 dynamics in response to acute laboratory mental stress (without physical exertion), evaluated diurnal changes using home saliva collections upon awakening and 45 minutes post-waking, and correlated salivary GDF15 levels with neurological symptoms, fatigue, and functional capacity.
What was found
Blood and saliva GDF15 levels were significantly higher in both mitochondrial disease groups compared to controls (p < 0.0001). GTEx profiling localized high GDF15 expression to salivary gland secretory cells. Salivary GDF15 increased in response to acute mental stress in both groups, whereas plasma GDF15 reactivity was blunted in mitochondrial disease patients relative to controls. Diurnally, salivary GDF15 peaked at awakening and dropped rapidly by 61.2% within 45 minutes, remaining elevated across the day in affected individuals. Salivary GDF15 correlated with neurological symptoms, fatigue, and functional capacity, and stress-evoked GDF15 changes increased the effect sizes of these symptom associations.
Why it matters
Establishes saliva as a viable, non-invasive biofluid for measuring GDF15 dynamics in mitochondrial disease and reveals that GDF15 fluctuates with diurnal cycles and acute psychological stress.
Limits
The cohort was small (40 patients restricted to two specific mitochondrial genetic defects), and the exact number and characteristics of healthy controls were not specified in the abstract. Rapid diurnal fluctuations (a 61.2% drop in 45 minutes) could introduce substantial measurement variability if sampling times are not rigorously standardized. Long-term prognostic value and responsiveness to therapeutic interventions were not assessed.