The TNFα locus is altered in monocytes from patients with systemic lupus erythematosus

Kathleen E. Sullivan, April Suriano, Kelly Dietzmann, Janice Lin, Daniel Goldman, Michelle A. Petri

Research output: Contribution to journalArticle

Abstract

In systemic lupus erythematosus, TNFα is elevated in the serum and correlates with disease activity and triglyceride levels. The stimuli that drive TNFα in this setting are incompletely understood. This study was designed to evaluate monocyte chromatin at the TNFα locus to identify semi-permanent changes that might play a role in altered expression of TNFα. SLE patients with relatively quiescent disease (mean Physician Global Assessment = 0.6) and healthy controls were recruited for this study. TNFα expression was measured by intracellular cytokine staining of different monocyte subsets in patients (n = 24) and controls (n = 12). Histone acetylation at the TNFα locus was measured by chromatin immunoprecipitation using a normalized quantitative PCR in patients (n = 46) and controls (n = 24). There were no differences in the overall fractions of cells expressing CD14 in SLE patients compared to controls; however, the fraction of DR+/CD16+ cells expressing CD14 was slightly higher as was true in the monocyte subset defined by DR+/CD11b+. Within the monocyte population defined by physical characteristics and DR+/CD14+, TNFα expressing cells were more frequent in SLE patients compared to controls. Both the fraction of positive cells and the mean fluorescence intensity were higher in patients than controls. Consistent with this was the finding that monocytes from patients had increased TNFα transcripts and more highly acetylated histones at the TNFα locus compared to controls. Furthermore, patients with the highest levels of TNFα histone acetylation were more likely to have had consistently elevated erythrocyte sedimentation rates, and to have required cytotoxic use. Histone acetylation, associated with increased transcriptional competence of TNFα, may play a role in certain inflammatory aspects of the disease.

Original languageEnglish (US)
Pages (from-to)74-81
Number of pages8
JournalClinical Immunology
Volume123
Issue number1
DOIs
StatePublished - Apr 1 2007

Keywords

  • Epigenetics
  • Histone
  • Lupus
  • TNFα

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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