Background/Purpose: Our CureJM JDM Registry/Repository contains sequential samples of peripheral blood mononuclear cells (PBMCs) and sera obtained every 6 months from over 467 children with definite juvenile dermatomyositis (JDM). Recent international genome-wide association studies confirmed that the highest genetic association with JDM is the ancestral HLA locus on chromosome 6, shared with other autoimmune disease, but did not identify novel pathways with genome-wide significance. In our cohort, 7.9% of JDM patients have another autoimmune disease; psoriasis is the most prevalent with 9 cases (2.2%). The purpose of this study was to assay PBMC samples using RNA-Seq to find biomarkers of disease activity for JDM as well as psoriasis.

Methods: After informed consent, PBMCs were obtained from 4 M and 5 F JDM patients (mean age <7), along with 2 M and 2 F controls (mean age 13.5). Of the JDM, 4 had JDM alone, 5 had JDM initially and later in their disease course developed psoriasis; all were tested versus the 4 controls. We utilized 18 total samples from the 9 JDM patients and 4 controls for RNA extraction and stranded RNA-Seq. We aligned the data to GRCh38 with STAR and analyzed differential expression using different strategies, including cuffdiff2, DESeq2, and edgeRun.

Results: Both the JDM-only and JDM pre-psoriasis samples show increased fold-changes (FC) compared to control samples for both CD69 (FC ≥ 3.5) which may be a signal of T cell proliferation and CD83 (FC ≥ 6), a marker enriched on mature dendritic cells. In the pre-psoriatic samples the significant changes included increases in the transcription factors ATF3 (FC ≥ 9) and NR4A1 (FC ≥ 4), as well as IL1B (FC ≥ 10) and Fos ligand (FOSL1; FC ≥ 20), in addition to genes associated with TNFα and NFκB signaling as determined by Gene Ontology, Corum, and KEGG annotations. At the time of psoriatic symptoms, the expression of CD69 had normalized in some patients with previous JDM. The post-psoriatic samples were similar to controls and the majority of the JDM inflammatory signatures had resolved.

Conclusion: 1) Upregulation of CD69, CD83, along with increased TNFα and NFκB signaling, are components of the pathophysiology of JDM which may resolve as the disease subsides; 2) In the pre-psoriasis state, upregulation of transcription factors ATF3 and NR4A1, as well as IL1B and FOSL1were documented.

Speculation: These gene expression patterns could represent biomarkers for the evolution of phases of JDM clinical activity, but increased sample size is needed to fully differentiate the JDM and psoriatic signatures.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/mining-rna-seq-of-peripheral-blood-mononuclear-cells-from-jdm-alone-compared-with-jdm-plus-psoriasis-for-biomarkers-of-disease-activity/