J Transl Med 2019 05 14;17(1):157. Epub 2019 May 14.
Radboud Expertise Center for Q Fever, Department of Internal Medicine, Division of Infectious Diseases 463, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Background: Q fever fatigue syndrome (QFS) is a well-documented state of prolonged fatigue following around 20% of acute Q fever infections. It has been hypothesized that low grade inflammation plays a role in its aetiology. In this study, we aimed to identify transcriptome profiles that could aid to better understand the pathophysiology of QFS.
Methods: RNA of monocytes was collected from QFS patients (n = 10), chronic fatigue syndrome patients (CFS, n = 10), Q fever seropositive controls (n = 10), and healthy controls (n = 10) who were age- (± 5 years) and sex-matched. Transcriptome analysis was performed using RNA sequencing.
Results: Mitochondrial-derived peptide (MDP)-coding genes MT-RNR2 (humanin) and MT-RNR1 (MOTS-c) were differentially expressed when comparing QFS (- 4.8 log2-fold-change P = 2.19 × 10 and - 4.9 log2-fold-change P = 4.69 × 10), CFS (- 5.2 log2-fold-change, P = 3.49 × 10 - 4.4 log2-fold-change, P = 2.71 × 10), and Q fever seropositive control (- 3.7 log2-fold-change P = 1.78 × 10 and - 3.2 log2-fold-change P = 1.12 × 10) groups with healthy controls, resulting in a decreased median production of humanin in QFS patients (371 pg/mL; Interquartile range, IQR, 325-384), CFS patients (364 pg/mL; IQR 316-387), and asymptomatic Q fever seropositive controls (354 pg/mL; 292-393).
Conclusions: Expression of MDP-coding genes MT-RNR1 (MOTS-c) and MT-RNR2 (humanin) is decreased in CFS, QFS, and, to a lesser extent, in Q fever seropositive controls, resulting in a decreased production of humanin. These novel peptides might indeed be important in the pathophysiology of both QFS and CFS.