Monozygotic twins discordant for juvenile dermatomyositis: clinical, serological and gene expression studies.

Abstract

Background: Juvenile Dermatomyositis (JDM) is a rare pediatric autoimmune disease involving a combination of environmental and genetic susceptibility factors. Monozygotic twins provide a unique opportunity to examine disease-specific gene expression as they share the same DNA. The goal of this study is to characterize gene expression differences between monozygotic twins discordant for JDM.

Methods: Five pairs of monozygotic twins were included. Each twin set was discordant for JDM. Detailed clinical and laboratory assessments were performed at enrollment. Nailfold capillary end row loops (ERL) count was obtained for all study subjects. Serum levels of cytokines and chemokines were measured using the Meso Scale Discovery^® technique. Three pairs of twins had their peripheral blood mononuclear cells (PBMCs) tested by RNASeq.

Results: The JDM twin had significantly lower nailfold capillary ERL than the healthy control, and two non-JDM twins also had decreased ERL In addition, serum endoglin was significantly lower in both JDM and non-JDM twins than in the healthy control. RNASeq identified four genes differentially expressed between the JDM and non-JDM twins: DCD, KRT14, COL1A1, and COL3A1.

Conclusions: JDM twins (and two of the non-JDM twins) had significantly lower nailfold capillary ERL and decreased serum endoglin levels compared to healthy controls. Further studies are needed to explore the role of the differentially expressed genes (DCD, KRT14, COL1A1, and COL3A1) in the pathophysiology of JDM.