Molecular endotypes of type 1 and type 2 SLE.

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.