Session Type: Abstract Submissions (ACR)
Background/Purpose: To date, gene expression profiling has not been performed in Erdheim-Chester disease (ECD), a rare, non-Langerhans form of histiocytosis. The aim of this study was to analyze the transcriptome of ECD compared to healthy individuals, as a manner to identify new pathways involved in the pathogenesis of the disease as well as new therapeutic targets.
Methods: Total RNA was extracted from peripheral blood mononuclear cell (PBMC) obtained in 58 patients with biopsy-proven ECD and 36 healthy individuals. Complementary DNA (cDNA) was hybridized in Illumina Human HT-12® v4 Expression Bead Chips. Statistical analysis of Microarray (SAM) algorithm with Benjamini and Hochberg multiple testing correction was used to determine the statistical significance of the differences in gene expression while controlling the false-discovery rate. Cluster analysis was also performed with JMP8 software. Differentially expressed genes were analyzed to identify potential functional pathways using Ingenuity® Pathway Analysis (IPA).
Results: Gene expression analysis using SAM showed 265 significantly down- or up-regulated transcripts between ECD patients and controls. Cluster analysis of these transcripts by similarity on gene expression patterns identified several clusters containing only ECD patients, healthy individuals, or both, underlining the strong heterogeneity of the disease. The set of genes statistically different between ECD and healthy individuals was further analyzed with IPA Analysis, which revealed a role for genes related to growth factor and cytokine activities, cyclin-dependant cell-cycle genes, regulation of phosphate homeostasis, DNA packaging, transcription regulation, and mRNA stability.
Conclusion: This large multicenter collaborative transcriptome analysis of 58 patients with Erdheim-Chester disease reveals that complex gene expression patterns are involved in the pathogenesis of the disease. This may be seen as a significant advance in this rare disease with poor prognosis and non-formally codified therapeutic management.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/whole-transcriptome-analysis-in-erdheim-chester-disease-a-multicenter-collaborative-study-of-58-patients/