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01.12.2019 | Research | Ausgabe 1/2019 Open Access

Journal of Translational Medicine 1/2019

A possible role for mitochondrial-derived peptides humanin and MOTS-c in patients with Q fever fatigue syndrome and chronic fatigue syndrome

Zeitschrift:
Journal of Translational Medicine > Ausgabe 1/2019
Autoren:
Ruud P. H. Raijmakers, Anne F. M. Jansen, Stephan P. Keijmel, Rob ter Horst, Megan E. Roerink, Boris Novakovic, Leo A. B. Joosten, Jos W. M. van der Meer, Mihai G. Netea, Chantal P. Bleeker-Rovers
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12967-019-1906-3) contains supplementary material, which is available to authorized users.

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Abstract

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 × 10−9 and − 4.9 log2-fold-change P = 4.69 × 10−8), CFS (− 5.2 log2-fold-change, P = 3.49 × 10−11 − 4.4 log2-fold-change, P = 2.71 × 10−9), and Q fever seropositive control (− 3.7 log2-fold-change P = 1.78 × 10−6 and − 3.2 log2-fold-change P = 1.12 × 10−5) 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.
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