title: Plasma levels of advanced glycation end products are associated with haemolysis-related organ complications in sickle cell patients.
abstract: Oxidative stress plays an important role in the pathophysiology of sickle cell disease (SCD). Plasma levels of advanced glycation end products (AGEs) are increased under oxidative conditions and are associated with disease severity in diabetes and inflammatory diseases. We investigated whether AGEs are increased in sickle cell patients and whether they are associated with SCD-related complications. Plasma levels of the AGEs pentosidine, N(ε) -(carboxymethyl)lysine (CML) and N(ε) -(carboxyethyl)lysine (CEL) were measured using single-column high performance liquid chromatography with fluorescence detection (pentosidine) and ultra performance liquid chromatography-tandem mass spectrometry (CML and CEL). Plasma levels of pentosidine and CML were increased in HbSS/HbSβ⁰-thalassaemia (n=60) and HbSC/HbSβ(+) -thalassaemia (n=42) patients during steady state as compared to healthy HbAA controls (n=30) without increments during painful crisis. CEL levels were comparable between all groups. Pentosidine and CML levels correlated significantly to haemolytic rate during the clinically asymptomatic state while pentosidine was significantly related to the number of haemolysis-related organ complications. The increased plasma AGE levels in sickle cell patients and their association with haemolysis and haemolysis-related complications suggest AGEs might be implicated in the pathophysiology of the haemolytic phenotype of SCD. Measurement of AGEs might be useful in predicting organ complications in SCD.
authors.affiliation: Department of Internal Medicine, Slotervaart Hospital Department of Haematology Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Erfan
authors.initials: E
authors.lastname: Nur
authors.forename: Dees P
authors.initials: DP
authors.lastname: Brandjes
authors.forename: John-John B
authors.initials: JJ
authors.lastname: Schnog
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Otten
authors.forename: Karin
authors.initials: K
authors.lastname: Fijnvandraat
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; C067242:N(epsilon)-(carboxymethyl)hydroxylysine; C054688:N(6)-(1-carboxyethyl)lysine; D001120:Arginine; C062187:pentosidine; D008239:Lysine