624 The Molecular Endotypes of Type 1 and Type 2 SLE

Abstract

Objective

To characterize the molecular landscape of patients with Type 1 and Type 2 systemic SLE erythematosus (SLE) by analyzing 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 manifestations of Type 1 and Type 2 SLE as determined by SLE Disease Activity Index (SLEDAI) and Polysymptomatic Distress (PSD) score, respectively. The top 5,000 row variance genes were analyzed by a suite of gene expression technologies to generate gene coexpression modules which were functionally annotated and correlated to various demographic traits, clinical features and laboratory assays.

Results

Stable k-means clustering of gene coexpression modules effectively segregated Type 1 from Type 2 SLE. Unique Type 1 SLE enrichments included IFN, neutrophils, monocytes, IL-1, TNF, cell cycle, and neurotransmitter pathways, whereas unique Type 2 SLE enrichments included B cells, plasma cells, Ig chains, and neuromuscular pathways. Enrichment of the IFN signature was not observed in Type 2 SLE. Gene expression patterns of some Type 2 SLE patients were identified amongst gene expression profiles reported in the literature for inactive SLE and idiopathic fibromyalgia (FM) patients.

Conclusion

A suite of orthogonal gene coexpression technologies 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.