The Molecular Endotypes of Type 1 and Type 2 SLE

Abstract

ABSTRACTObjectiveTo characterize the molecular landscape of patients with Type 1 and Type 2 systemic SLE erythematosus (SLE) by analyzing gene expression profiles from peripheral blood.MethodsFull 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 5,000 row variance genes were analyzed by Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) to generate gene co-expression modules, that were functionally annotated and correlated to various demographic traits, clinical features and laboratory measures.ResultsExpression of specific gene coexpression modules correlated with individual features of Type 1 and 2 SLE and also effectively segregated samples from Type 1 from Type 2 SLE patients. Unique Type 1 SLE enrichments included IFN, monocytes, T cells, cell cycle, and neurotransmitter pathways, whereas unique Type 2 SLE enrichments included B cells and metabolic and neuromuscular pathways. Gene co-expression modules of Type 2 SLE patients 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.ConclusionGene 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.