Molecular endotypes of type 1 and type 2 SLE

Lupus Sci Med. 2023 Jan;10(1):e000861. doi: 10.1136/lupus-2022-000861.

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.

Keywords: autoimmune diseases; fibromyalgia; inflammation; lupus erythematosus, systemic.

MeSH terms

  • Fatigue
  • Fibromyalgia*
  • Gene Expression Profiling
  • Humans
  • Lupus Erythematosus, Systemic* / genetics
  • RNA

Substances

  • RNA