Background Cutaneous lupus erythematosus (CLE) and dermatomyositis (DM) are autoimmune diseases with characteristic cutaneous rashes. Both are histopathologically characterized by interface dermatitis and they are difficult and sometimes impossible to differentiate based on skin biopsies. The specific pathogenesis of both conditions remains enigmatic.
Methods Punch biopsies were obtained from lesional skin from patients with CLE (n=6) or DM (n=5), and control skin (n=6). Equal volumes of tissue were microdissected within the CLE and DM dermal inflammatory infiltrates and control dermis. Proteomic database was constructed using nano-LC tandem mass spectrometry. Qiagen Ingenuity pathway analysis was performed, and identified canonical pathways were compared between CLE, DM, and controls.
Results Comparing CLE vs controls we identified 246 pathways, while 51 of them were enriched (threshold p<0.05). Comparing DM vs controls 200 pathways were identified, 72 enriched. Canonical pathways enriched in both CLE and DM were those involved in antigen presentation, protein ubiquitination, acute phase response, interferon signaling, GP6 signaling, tRNA charging, and B cell development. Analysis of CLE vs DM showed 237 pathways, 70 of them enriched (p<0.05). The top differentially enriched canonical pathways in CLE compared to DM included EIF2 signaling, complement system, LXR/RXR and FXR/RXR activation, acute phase response signaling, mTOR and granzyme A signaling, clathrin mediated endocytosis signaling, and coagulation system.
Conclusions Canonical pathways enriched in both CLE and DM skin are associated with activation of innate and adaptive immune systems, including the interferon system. A major difference between CLE and DM was that the EIF2 pathway, involved in cellular stress and induction of cell death, was enriched in CLE. Enhanced granzyme A signaling in CLE coincides with the top upregulated cytokine in the CLE proteomics being IL-16,1 majorly expressed by CD8 T lymphocytes. Further, results indicate differentially activated metabolic pathways and deposition of complement and coagulation components in CLE dermal infiltrate.
Niewold TB, Meves A, Lehman JS, et al. Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE. Arthritis Res Ther 2021;23:132. doi:10.1186/s13075-021-02511-0
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