Abstract
In juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, weakness is accompanied by a characteristic rash that often becomes chronic and is associated with vascular damage. We hoped to understand the molecular underpinnings of JDM, particularly when untreated, which would facilitate the identification of novel mechanisms and clinical targets that might disrupt disease progression. We studied the RNA-Seq data from untreated JDM peripheral blood mononuclear cells (PBMCs; n = 11), PBMCs from a subset of the same patients when clinically inactive (n = 8/11), and separate samples of untreated JDM skin and muscle (n = 4 each). All JDM samples were compared to non-inflammatory control tissues. The untreated JDM PBMCs showed a strong signature for type1 interferon response, along with IL-1, IL-10, and NF-κB. Surprisingly, PBMCs from clinically inactive JDM individuals had persistent immune activation that was enriched for IL-1 signaling. JDM skin and muscle both showed evidence for type 1 interferon activation and genes related to antigen presentation and decreased expression of cellular respiration genes. Additionally, we found that PBMC gene expression correlates with disease activity scores (DAS; skin, muscle, and total domains) and with nailfold capillary end row loop number (an indicator of microvascular damage). This included otoferlin, which was significantly increased in untreated JDM PBMCs and correlated with all 3 DAS domains. Overall, these data demonstrate that PBMC transcriptomes are informative of molecular disruptions in JDM and provide transcriptional evidence of chronic inflammation despite clinical quiescence.
Original language | English (US) |
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Article number | 275 |
Journal | Scientific reports |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2022 |
Funding
The authors would like to thank the patients who participated in this study, as well as the other physicians who helped care for these patients (K. Ardalan and M.L. Curran). We also thank Maria Amoruso for her help with control recruitment. We also thank the Department of Pediatric Orthopedics at the Ann & Robert H. Lurie Children’s Hospital of Chicago for their assistance in obtaining control skin and muscle. This work was supported in part by NIH Grants R21-AR066846 (LMP), P30-AR048335 (EDOR, LC), and P30-AR073752 (EDOR), as well as a grant from the Cure JM Foundation (LMP). The Genome Technology Access Center at Washington University generated the sequencing data and is supported by Siteman Cancer Center grant P30CA91842 and ICTS/CTSA Grant UL1TR000448. Some analyses were performed on the Center for High-Performance Computing (CHPC) cluster at Washington University, which is partially supported by NIH Grant S10 OD018091.
ASJC Scopus subject areas
- General