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Discoid lupus erythematosus (DLE) is the most common form of cutaneous lupus1. It can cause permanent scarring. The pathophysiology of is not fully understood. Plasmacytoid dendritic cells are found in close association with apoptotic keratinocytes inferring close cellular signalling. Matrix Associated Laser Desorption Ionisation (MALDI) combined with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS) is an exquisitely sensitive combination to examine disease processes at the cellular and molecular level. Active areas of discoid lupus erythematosus were compared with normal perilesional skin using MALDI combined with FT-ICR-MS. A unique set of biomarkers, including epidermal lipids is identified in active discoid lupus. These were assigned as sphingomyelins, phospholipids and ceramides. Additionally, increased levels of proteins from the keratin, and small proline rich family, and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) in the epidermis are observed. These techniques, applied to punch biopsies of the skin, have shown a distinctive lipid profile of active discoid lupus. This profile may indicate specific lipid signalling pathways. Lipid rich microdomains (known as lipid rafts) are involved in cell signalling and lipid abnormalities have been described with systemic lupus erythematosus which correlate with disease activity. [ABSTRACT FROM AUTHOR]