Molecular endotypes of type 1 and type 2 SLE. Issue 1 (30th January 2023)

• Record Type: Journal Article
• Authors: Robl, Robert; Eudy, Amanda; Bachali, Prathyusha S; Rogers, Jennifer L; Clowse, Megan; Pisetsky, David; Lipsky, Peter
• Is Part Of: Lupus science & medicine. Volume 10:Issue 1(2023)
• Publication Date: 2023-01-30
• Subjects: lupus erythematosus, systemic -- fibromyalgia -- autoimmune diseases -- inflammation; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2022-000861
• Languages: English
• ISSNs: 2398-8851

Abstract

Abstract : Objective: To character the molecular landscape of patients with type 1 and type 2 SLE by analysing gene expression profiles from peripheral blood. Methods: Full transcriptomic RNA sequencing was carried out on whole blood samples from 18 subjects with SLE selected by the presence of manifestations typical of type 1 and type 2 SLE. The top 5000 row variance genes were analysed by Multiscale Embedded Gene Co-expression Network Analysis to generate gene co-expression modules that were functionally annotated and correlated with various demographic traits, clinical features and laboratory measures. Results: Expression of specific gene co-expression modules correlated with individual features of type 1 and type 2 SLE and also effectively segregated samples from patients with type 1 SLE from those with type 2 SLE. Unique type 1 SLE enrichment included interferon, monocytes, T cells, cell cycle and neurotransmitter pathways, whereas unique type 2 SLE enrichment included B cells and metabolic and neuromuscular pathways. Gene co-expression modules of patients with type 2 SLE were identified in subsets of previously reported patients with inactive SLE and idiopathic fibromyalgia (FM) and also identified subsets of patients with active SLE with a greater frequency of severe fatigue. Conclusion: Gene co-expression analysis successfully identified unique transcriptional patterns that segregate type 1 SLE from type 2 SLE and further identified type 2 molecular features in patients with inactive SLE or FM and with active SLE with severe fatigue.