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Journal article
MALDI-MSI Reveals Shared Lipid Signatures in Sarcoid-Like Granulomas of Mice and in a Human Case
American Journal of Physiology: Cell Physiology, Vol.329(3), pp.C768-C778
2025
PMID: 40668560
Abstract
Rationale
Sarcoidosis is a complex inflammatory disease of unknown cause, with diagnosis often complicated by a lack of definitive biomarkers. This study employed Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) to spatially profile lipids in sarcoid-like granulomatous tissues from animal and human samples.
Methods
ApoE-/- mice (n=23) were fed a cholate-containing high-fat diet for 16 weeks, inducing sarcoid-like granulomas. Granulomas were characterized through haematoxylin and eosin, Masson‘s Trichrome, and immunofluorescence staining, while lipidomic profiling of mouse hearts (n=10) and lymph nodes (n=10) was performed using MALDI-MSI. A comparative analysis was performed using a human sarcoid-like granulomatous lymph node.
Results
The mouse model exhibited granulomas, characterized by lipid-laden macrophages, fibrosis, and perivascular lymphocyte clusters. Human lymph nodes with sarcoid-like granulomas demonstrated hallmarks of sarcoidosis, including foamy histiocytes, non-necrotizing granulomas, and Langhans giant cells containing silicone and asteroid bodies. MALDI-MSI identified over 30 lipids that were consistently detected in murine heart and lymph node tissues. Of these, eight key lipids, belong to the Lysophosphatidylinositol (LPI), Phosphatidic acid (PA), Phosphatdylinositide (PI) and Phosphatidylserine (PS) classes, that were also detected in human lymph nodes.
Conclusions
To our knowledge, this is the first application of MALDI-MSI in spatial lipidomic profiling in sarcoid-like animal model and human sarcoid-like granulomatous tissue. MALDI-MSI revealed distinct yet shared lipidomic profiles in both sarcoid-like animal and human tissues. This finding provides a new perspective in sarcoidosis pathogenesis and warrants future mechanistic study and validation.
Details
- Title
- MALDI-MSI Reveals Shared Lipid Signatures in Sarcoid-Like Granulomas of Mice and in a Human Case
- Authors/Creators
- Junwoo Kim - School of Medicine, The University of Western Australia, AustraliaYuben Moodley - Fiona Stanley HospitalNick S R Lan - Fiona Stanley HospitalShelley Waters - The University of Western AustraliaDana Hicks - Computational and Systems Medicine, Health Futures Institute, Murdoch UniversityHoi Sze Yeung - Murdoch UniversityNicola Gray - Murdoch UniversityJulien Wist - Murdoch UniversityFelicity Lee - Fiona Stanley HospitalBenjamin Allanson - Pathwest Laboratory MedicineLokesh Yagnik - Fiona Stanley HospitalFaridh Raja Mohamed - Fiona Stanley HospitalSilvia Lee - Harry Perkins Institute of Medical ResearchGirish Dwivedi - Harry Perkins Institute of Medical Research
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.329(3), pp.C768-C778
- Publisher
- American Physiological Society
- Identifiers
- 991005794528707891
- Copyright
- © 2025 The Authors
- Murdoch Affiliation
- Centre for Computational and Systems Medicine
- Language
- English
- Resource Type
- Journal article
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