Metabolomic and lipidomic profiling of granuloma annulare lesional skin

Summary: Abstract Body: Granuloma annulare (GA) is an idiopathic, inflammatory skin condition characterized by granulomatous inflammation. GA is associated with systemic metabolic dysfunction including diabetes and dyslipidemia. Moreover, immune cell metabolic rewiring within granulomatous inflammation has been shown to support granuloma formation and propagation. Despite this, there has been little investigation into immunometabolic mechanisms in GA pathology. Here, we perform metabolomics and lipidomics on skin biopsies from GA lesional skin and contralateral non-lesional biopsies from 20 subjects. We combine these data with subjects’ clinical data and previously generated spatial transcriptomics data to profile metabolism in GA lesional skin. We discovered that GA lesional skin had a unique metabolic profile with significant modulation of 32/103 identified polar metabolites and 85/314 identified lipids. We discovered significant accumulation of kynurenine and loss of its receptor in GA lesional skin. Pentose phosphate pathway and purine metabolism intermediates accumulate in GA lesional skin, consistent with activation of pro-inflammatory macrophages. Lastly, there is accumulation of polyunsaturated phospholipids suggesting increased synthesis of inflammatory signaling mediators. Using this data, we aim to build a foundation for future studies on the mechanisms of metabolic regulation driving GA pathology and identify new therapeutic targets for GA and other granulomatous diseases. Jorgo Lika^{1, 2, 3}, Chitrasen Mohanty⁴, Christina Kendziorski⁴, Jing Fan^{1, 2}, Bridget E. Shields⁵ 1. Morgridge Institute for Research, Madison, WI, United States. 2. Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, United States. 3. Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI, United States. 4. Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, United States. 5. Department of Dermatology, University of Wisconsin-Madison, Madison, WI, United States. Translational Studies: Cell and Molecular Biology