Transcriptomic analysis reveals immune signatures associated with specific cutaneous manifestations of lupus in systemic lupus erythematosus
Lee, E. Y.; Patterson, S.; Cutts, Z.; Lanata, C. M.; Dall'Era, M.; Yazdany, J.; Criswell, L. A.; Haemel, A.; Katz, P.; Ye, C. J.; Langelier, C.; Sirota, M.
Show abstract
Systemic lupus erythematosus (SLE) presents with diverse heterogenous cutaneous manifestations. However, the molecular and immunologic pathways driving specific cutaneous manifestations of SLE are poorly understood. Here, we leverage transcriptomics from a large well-phenotyped longitudinal cohort of SLE patients to map molecular pathways linked to ten distinct SLE-related rashes. Through whole blood and immune cell-sorted bulk RNA sequencing, we identified immune signatures specific to cutaneous subtypes of SLE. Subacute cutaneous lupus (SCLE) exhibited broad upregulation of interferon, TNF-, and IL6-JAK-STAT3 pathways suggesting potential unique therapeutic responses to JAK and type I interferon inhibition. While interferon signaling is prominent in SCLE, discoid lupus, and acute lupus, it is unexpectedly attenuated in patients with skin and mucosal ulcers. Pathway and cell-type enrichment analysis revealed unexpected roles for CD14+ monocytes in photosensitivity of SLE and NK cells in alopecia, mucosal ulceration, and livedo reticularis. These findings illuminate the immune heterogeneity of rashes in SLE, highlighting subtype-specific mechanistic targets, and presenting opportunities for precision therapies for SLE-associated skin phenotypes.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney 98%
- Patient ancestry significantly contributes to molecular heterogeneity of systemic lupus erythematosus. 94%
- Coordinated immune dysregulation in Juvenile Dermatomyositis revealed by single-cell genomics 94%
Similar papers in this journal
- SAP expressing T peripheral helper cells identify systemic lupus erythematosus patients with lupus nephritis 96%
- Interleukin-36 upregulates type-I interferon responses in systemic lupus erythematosus by promoting the accumulation of self-nucleic acids 95%
- Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients 94%
Similar papers in this journal
- Plasmacytoid dendritic cells are functionally exhausted while non-haematopoietic sources of type I interferon dominate human autoimmunity 94%
- SLE non-coding Genetic Risk Variant Determines the Epigenetic Dysfunction of an Immune Cell Specific Enhancer that Controls Disease-critical microRNA Expression 91%
- Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis 91%
Similar papers in this journal
- Context-dependent miR-21 regulation of TLR7-mediated autoimmune and foreign antigen driven antibody-forming cell and germinal center responses 95%
- The complement regulator CD55 modulates TLR9 signaling and supports survival in marginal zone B cells 92%
- Elevated N-glycosylation of immunoglobulin G variable regions in myasthenia gravis highlights a commonality across autoantibody-associated diseases 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.