Abstract
BackgroundThe objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM).MethodsSkin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC).ResultsProteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions.ConclusionsUsing unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.
Highlights
The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM)
Total protein analysis of inflammatory foci in CLE and DM We analyzed the total proteome of excised inflammatory foci of CLE and DM lesions in order to identify the upregulated proteins of major importance
The unbiased total proteome analysis identified over 2000 proteins that were detected at a level of at least 5 copies per sample
Summary
The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM). Systemic lupus erythematosus (SLE) is an autoimmune disease with a range of clinical manifestations including systemic inflammation, circulating autoantibodies against nuclear antigens and other intracellular molecules, and frequent involvement of the skin, joints, and renal and hematological systems. Cutaneous lupus erythematosus (CLE) is one of the specific manifestations of SLE and may develop in patients without systemic disease. The autoimmune inflammation observed in SLE and CLE is a result of activated inflammatory pathways within both the innate and adaptive immune systems, and interferons (IFNs) are thought to be the key mediators [3]. Dermatomyositis (DM) is another systemic autoimmune disease, primarily affecting the muscles and skin. In DM, anti-nuclear antibodies are common, as are autoantibodies directed against tRNA synthetases [5]
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