Trusted Resources: Evidence & Education
Scientific literature and patient education texts
Iron, inflammation, and early death in adults with sickle cell disease
source: Circulation Research
year: 2015
authors: van Beers EJ, Yang Y, Raghavachari N, Tian X, Allen DT, Nichols JS, Mendelsohn L, Nekhai S, Gordeuk VR, Taylor JG 6th, Kato GJ
summary/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<0.001). Further linking intracellular iron and inflammation, 14 SCD patients with a ferroportin Q248H variant that causes intracellular iron accumulation had significantly higher levels of interleukin-6 and C-reactive protein compared with 14 matched SCD patients with the wild-type allele (P<0.05). Finally, in a cohort of 412 patients followed for a median period of 47 months (interquartile range, 24-82), C-reactive protein was strongly and independently associated with early death (hazard ratio, 3.0; 95% confidence interval, 1.7-5.2; P<0.001).
CONCLUSIONS:
Gene expression markers of high intracellular iron in patients with SCD are associated with markers of inflammation and mortality. The results support a model in which intracellular iron promotes inflammatory pathways, such as the TLR system and the inflammasome, identifying important new pathways for additional investigation.
DOI: 10.1161/CIRCRESAHA.116.304577
read more full text
Related Content
-
Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are...INTRODUCTION: Patients with sickle cell...
-
Sickle Cell Speaks: Misconceptions About the Diseasehttps://www.youtube.com/watch?v=tSEEZj9o...
-
Sickle Cell Disease and Its Toll Compared in Different Age Groups in StudyDifferences in comorbidities, pain, heal...
-
MARAC Advisory Statement: Update About COVID-19December 23, 2021 – The Sickle Cell Di...
-
A systematic review of the literature for severity predictors in children with sickle cell anemiaAll patients with HbSS (SCA) share the s...
-
Black Americans With Sickle Cell Trait At Increased Risk Of Kidney DiseaseAfrican Americans with sickle cell trait...
-
New digital education platform for the SCD communityhttps://www.onescdvoice.com/wp-content/u...
To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences. More Information
The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.