Project description:Background Giant cell arteritis (GCA) is a prevalent, intractable, granulomatous, large-vessel vasculitis. The pathologic features include destruction of the tunica media, infiltrating macrophages and multinucleated giant cells (MNGCs), immune responses associated with CD4+ T cells, accumulation of myofibroblasts, and hypertrophy of the intima. Objectives The molecular pathology of GCA has largely remained elusive, while the morphological features are well defined. We aimed to identify key molecules associated with the pathogenesis of GCA. Method Arterial lesions were obtained through temporal artery biopsy from 16 patients, including those diagnosed as GCA and not. The obtained samples underwent genome-wide gene expression profiling. The resulting data were examined to reveal specific pathways and genes, and some of the molecules were followed up by immunohistochemistry. Results GCA lesions had a distinguishing pattern of gene expression, including enrichment of immune cells and phagocytic pathways related to microglia and osteoclasts. We found MMP12 (macrophage elastase), HLA-DRA, phagocytosis- and osteoclast-associated molecules in infiltrating macrophages and MNGCs. We also found LRRC15-expressing cells in the tunica intima, suggesting a myofibroblast subpopulation that suppresses cytotoxic CD8+ T cells. These molecules were often upregulated in other granulomatous diseases affecting not only arteries but also lymph nodes. Conclusion Infiltrating macrophages and MNGCs expressed molecules that contribute to the pathogenetic features of GCA, including degradation of the tunica medium, induction of immune responses, and accumulation of myofibroblasts. The extended list of key molecules provides a solid baseline of elucidating the pathogenesis of GCA and developing therapeutic strategies.

2025-05-07 | GSE267979 | GEO

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