Iron, inflammation, and early death in adults with sickle cell disease

Eduard J. Van Beers, Yanqin Yang, Nalini Raghavachari, Xin Tian, Darlene T. Allen, James S. Nichols, Laurel Mendelsohn, Sergei Nekhai, Victor R. Gordeuk, James G. Taylor, Gregory J. Kato

Research output: Contribution to journalArticle

Abstract

RATIONALE:: Patients with sickle cell disease (SCD) have markers of chronic inflammation, but the mechanism of inflammation and its relevance to patient survival are unknown. OBJECTIVE:: To assess the relationship between iron, inflammation, and early death in SCD. METHODS AND RESULTS:: Using peripheral blood mononuclear cell transcriptome profile hierarchical clustering, we classified 24 patients and 10 controls in clusters with significantly different expression of genes known to be regulated by iron. Subsequent gene set enrichment analysis showed that many genes associated with the high iron cluster were involved in the toll-like receptor system (TLR4, TLR7, and TLR8) and inflammasome complex pathway (NLRP3, NLRC4, and CASP1). Quantitative PCR confirmed this classification and showed that ferritin light chain, TLR4, and interleukin-6 expression were >100-fold higher in patients than in controls (P

Original languageEnglish (US)
Pages (from-to)298-306
Number of pages9
JournalCirculation Research
Volume116
Issue number2
DOIs
StatePublished - Jan 16 2015
Externally publishedYes

Fingerprint

Sickle Cell Anemia
Iron
Inflammation
Apoferritins
Inflammasomes
Toll-Like Receptors
Transcriptome
Genes
Cluster Analysis
Interleukin-6
Blood Cells
Gene Expression
Polymerase Chain Reaction
Survival

Keywords

  • gene expression
  • inflammation
  • iron
  • mortality
  • sickle cell disease

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Van Beers, E. J., Yang, Y., Raghavachari, N., Tian, X., Allen, D. T., Nichols, J. S., ... Kato, G. J. (2015). Iron, inflammation, and early death in adults with sickle cell disease. Circulation Research, 116(2), 298-306. https://doi.org/10.1161/CIRCRESAHA.116.304577

Iron, inflammation, and early death in adults with sickle cell disease. / Van Beers, Eduard J.; Yang, Yanqin; Raghavachari, Nalini; Tian, Xin; Allen, Darlene T.; Nichols, James S.; Mendelsohn, Laurel; Nekhai, Sergei; Gordeuk, Victor R.; Taylor, James G.; Kato, Gregory J.

In: Circulation Research, Vol. 116, No. 2, 16.01.2015, p. 298-306.

Research output: Contribution to journalArticle

Van Beers, EJ, Yang, Y, Raghavachari, N, Tian, X, Allen, DT, Nichols, JS, Mendelsohn, L, Nekhai, S, Gordeuk, VR, Taylor, JG & Kato, GJ 2015, 'Iron, inflammation, and early death in adults with sickle cell disease', Circulation Research, vol. 116, no. 2, pp. 298-306. https://doi.org/10.1161/CIRCRESAHA.116.304577
Van Beers EJ, Yang Y, Raghavachari N, Tian X, Allen DT, Nichols JS et al. Iron, inflammation, and early death in adults with sickle cell disease. Circulation Research. 2015 Jan 16;116(2):298-306. https://doi.org/10.1161/CIRCRESAHA.116.304577
Van Beers, Eduard J. ; Yang, Yanqin ; Raghavachari, Nalini ; Tian, Xin ; Allen, Darlene T. ; Nichols, James S. ; Mendelsohn, Laurel ; Nekhai, Sergei ; Gordeuk, Victor R. ; Taylor, James G. ; Kato, Gregory J. / Iron, inflammation, and early death in adults with sickle cell disease. In: Circulation Research. 2015 ; Vol. 116, No. 2. pp. 298-306.
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