IL-6 and TNF are Potential Inflammatory Biomarkers in Facioscapulohumeral Muscular Dystrophy.
J Neuromuscul Dis
; 11(2): 327-347, 2024.
Article
in En
| MEDLINE
| ID: mdl-38250782
ABSTRACT
Background:
FSHD is a highly prevalent inherited myopathy with a still poorly understood pathology.Objective:
To investigate whether proinflammatory cytokines are associated with FSHD and which specific innate immune cells are involved in its pathology.Methods:
First, we measured circulating cytokines in serum samples IL-6 (FSHD, nâ=â150; HC, nâ=â98); TNF (FSHD, nâ=â150; HC, nâ=â59); IL-1α (FSHD, nâ=â150; HC, nâ=â66); IL-1ß (FSHD, nâ=â150; HC, nâ=â98); MCP-1 (FSHD, nâ=â14; HC, nâ=â14); VEGF-A (FSHD, nâ=â14; HC, nâ=â14). Second, we tested trained immunity in monocytes (FSHD, nâ=â15; HC, nâ=â15) and NK cells (FSHD, nâ=â11; HC, nâ=â11). Next, we explored the cytokine production capacity of NK cells in response to different stimuli (FSHD, nâ=â39; HC, nâ=â22). Lastly, we evaluated the cytokine production of ex vivo stimulated MRI guided inflamed (TIRM+) and paired MRI guided non inflamed (TIRM-) muscle biopsies of 21 patients and of 8 HC muscle biopsies.Results:
We included a total of 190 FSHD patients (Nâ=â190, 48±14 years, 49% men) and of 135 HC (Nâ=â135, 44±15 years, 47% men). We found that FSHD patients had higher concentrations of IL-6 and TNF measured (a) in the circulation, (b) after ex-vivo stimulation of NK cells, and (c) in muscle specimens. Besides, IL-6 circulating concentrations, as well as its production by NK cells and IL-6 content of FSHD muscle specimens, showed a mild correlation with disease duration, disease severity, and muscle weakness.Conclusion:
These results show that IL-6 and TNF may contribute to FSHD pathology and suggest novel therapeutic targets. Additionally, the activation of NK cells in FSHD may be a novel pathway contributing to FSHD pathology.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Muscular Dystrophy, Facioscapulohumeral
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
J Neuromuscul Dis
/
J. Neuromuscul. Dis
/
Journal of neuromuscular diseases (Online)
Year:
2024
Document type:
Article
Affiliation country:
Países Bajos
Country of publication:
Países Bajos