Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Cutaneous lupus rashes can be substantial, disfiguring, and often refractory to usual lupus therapies. Phenotypic presentation and risk of systemic lupus manifestations differs by rash subtype and pathogenic factors contributing to rash remain poorly understood. For this study, we evaluated the transcriptional profiles of discoid lupus (DLE) and subacute cutaneous lupus (sCLE) rashes and characterized them in the context of contributing cellular populations and the unique profiles which may contribute to individual rash phenotype.
Methods: Formalin-fixed paraffin-embedded (FFPE) tissue blocks of 26 DLE and 27 sCLE rash biopsies were acquired from the University of Michigan Anatomic Pathology repository. RNA was isolated from five 10 micron sections and analyzed via Affymetrix ST 2.1 array. Gene expression changes were compared to 7 similarly treated and isolated healthy control biopsies. Genomatix, Ingenuity and in silico immunophenotyping were used for data analysis.
Results: Using q-value of <0.01 and|log Fold Change|>1 as filters, we identified 394 genes commonly upregulated and 175 genes commonly downregulated in sCLE and DLE compared to control. Genomatix analysis confirmed enhancement of known lupus-associated pathways (especially type I interferon (IFN) regulated genes), and transcription factor analysis revealed important gene regulation by STAT1, STAT4 and IRF1. Upregulation of TLR2 and inflammasome-associated genes were also noted. Immunophenotypic analysis demonstrated a significant proportion of upregulated genes were likely to be derived from myeloid cells within the skin. Alternatively, many of the downregulated genes were associated with keratinocytes. 173 genes were uniquely regulated in DLE and 116 genes were uniquely regulated in sCLE. Unique to DLE, a strong upregulation of IFN gamma associated pathways was noted and Ingenuity pathway analysis identified IL-4 as a likely prominent regulator of DLE-specific gene expression. In sCLE, type I IFN signaling predominated and unique expression of CD14 and the chemokines CCL20 and CCL2 were seen.
Conclusion: These data suggest that DLE and sCLE have overlapping and unique changes which may guide pathologic phenotype. Importantly, the role of myeloid populations in cutaneous lupus pathogenesis should be considered. Confirmation and further study of these identified dysregulated genes may identify targets for novel therapy of cutaneous lupus lesions.
To cite this abstract in AMA style:Berthier CC, Stannard J, Myers E, Swindell W, Lowe L, Reed TJ, Gudjonsson J, Kahlenberg JM. Transcriptional Profiling of Cutaneous Lupus Reveals Pronounced Changes in Keratinocyte and Myeloid Lineage Expressed Genes and Demonstrates Uniquely Regulated Interferon Pathways Between Rash Subtypes [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/transcriptional-profiling-of-cutaneous-lupus-reveals-pronounced-changes-in-keratinocyte-and-myeloid-lineage-expressed-genes-and-demonstrates-uniquely-regulated-interferon-pathways-between-rash-subtype/. Accessed June 1, 2020.
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