In this study we aim to elucidate the effects of inhibited lcFAO on monocyte phenotype and inflammatory activation.
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* monocyte phenotype, including monocyte subset percentages and their
expression of key surface proteins, including inflammatory and
anti-inflammatory markers and receptors
* Inflammatory responses, whole blood will be activated with the prototypical
pro-inflammatory TLR4 trigger LPS (lipopolysaccharide) and production of
cytokines will be assessed after 24 h (i.e. IL-6, TNF, IL-12, IL-8)
Secondary outcome
phenotype of other immune cells (e.g. neutrophils, T cells and B cells)
Background summary
Patients with a genetic defect in lcFAO can suffer from various symptoms
induced by catabolism, but rhabdomyolysis (excessive muscle breakdown) is most
frequently reported in adults and adolescents. The pathophysiology is still
poorly understood. Macrophages, a white blood cell, differentiate from blood
monocytes and perform both pro- and anti-inflammatory functions. The mechanisms
that control the functions of distinct macrophage subsets remain ill-defined,
especially in humans. Recent studies highlight the crucial role of metabolic
pathways including fatty acid oxidation in the regulation of macrophages (and
monocytes as their more immature precursors).We hypothesize that
pro-inflammatory capacities of macrophages could trigger muscle break down in
these patients. Using monocytes of lcFAO deficient (lcFAOd) patients, this
project aims to understand the role of lcFAO in regulating monocyte and
macrophage inflammatory responses. The attained knowledge will significantly
strengthen our fundamental understanding on the role of lcFAO in macrophage
regulation and will highlight to what extend these defects in monocytes and
macrophages can explain the clinical symptoms that the lcFAO deficient patients
experience. Moreover, the results might reveal possible therapeutic targets to
arrest the rhabdomyolysis cascade in an early stage, as this is near impossible
until date.
Study objective
In this study we aim to elucidate the effects of inhibited lcFAO on monocyte
phenotype and inflammatory activation.
Study design
Longitudinal invasive observational study
Study burden and risks
Venous blood will be drawn (maximum of 30 mL) for further investigation of the
monocyte phenotype and inflammatory activation. Preferably blood will be drawn
at times venous acces is already required for regular care. If this is not
feasible blood will be drawn by venapuncture. Venapuncture can be painful and
cause hematoma
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
-Enzymatically confirmed long-chain fatty acid oxidation disorder including
VLCAD, LCHAD, MTP, CPT1, CPT2 and CACT deficiency
-18 years old or older
Exclusion criteria
(auto-) immunedisorder
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL67564.018.18 |