MALDI-MSI reveals shared lipid signatures in sarcoid-like granulomas of mice and in a human case

Sarcoidosis is a complex inflammatory disease of unknown cause, with diagnosis often complicated by a lack of definitive biomarkers. This study used matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) to spatially profile lipids in sarcoid-like granulomatous tissues from animal and human samples. <i>ApoE</i>^-/- mice (<i>n</i> = 23) were fed a cholate-containing high-fat diet for 16 wk, inducing sarcoid-like granulomas. Granulomas were characterized through hematoxylin-eosin, Masson's trichrome, and immunofluorescence staining, whereas lipidomic profiling of mouse hearts (<i>n</i> = 10) and lymph nodes (<i>n</i> = 10) was performed using MALDI-MSI. A comparative analysis was performed using a human sarcoid-like granulomatous lymph node. 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, phosphatidic acid, phosphatidylinositide, and phosphatidylserine classes, which were also detected in human lymph nodes. To our knowledge, this is the first application of MALDI-MSI in spatial lipidomic profiling in a 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 on sarcoidosis pathogenesis and warrants future mechanistic study and validation.<b>NEW & NOTEWORTHY</b> This is the first study to apply MALDI-MSI to characterize the spatial lipidomic landscape of granulomatous inflammation in both a murine sarcoid-like model and a rare human case. Our work reveals distinct yet shared lipidomic profiles in both sarcoid-like animal and human tissues, including region-specific lipid alterations within granulomas. By integrating spatial imaging with lipidomics, this study bridges a critical gap in our understanding of the metabolic and structural composition of granulomatous inflammation.