223. CD163-mediated hemoglobin-scavenging system, haptoglobin phenotype and preeclampsia risk

Abstract

Introduction Preeclampsia (PE) is a multisystemic disorder which complex pathophysiology involves both oxidative stress and endothelial dysfunction as key factors. The CD163-mediated haptoglobin (HP) hemoglobin-scavenging system has been proposed as an important pathway for diverse disease states due to its anti-inflammatory and pro-angiogenic effects. The human HP locus is polymorphic, yielding three distinct phenotypes characterized by different antioxidant and pro-angiogenic properties. Objective We aimed to determine whether HP phenotype was associated with PE risk and to assess the relationship between HP phenotype and first-trimester concentrations of HP, soluble form of the hemoglobin-scavenger receptor CD163 (sCD163), placental growth-factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Methods Case-control study of 452 pregnant women selected from a prospective cohort of singleton pregnancies that underwent first-trimester aneuploidy screening in a routine care low-risk setting. The study sample included 204 women who subsequently developed PE and 248 women with normal pregnancies who were matched for gestational age. HP phenotypes were determined by polyacrylamide gel electrophoresis (PAGE). First-trimester serum PlGF, sFlt-1 and HP concentrations were determined by automated electrochemiluminescence/immunoturbidimetric methods (Roche Diagnostics), while sCD163 levels were determined by enzyme-linked immunosorbent assay (R&D Systems). Results Although HP phenotype alone did not affect overall PE risk, we found significantly higher HP concentrations between preeclamptic and normal women with HP2-1 (122.0/107.1 mg/dL, P = 0.01) and HP2-2 (101.0/82.0 mg/dL, P = 0.001) phenotypes. HP2-2 phenotype was also associated with high levels of sCD163 (472.6/418.6 ng/mL, P = 0.02) that were significantly higher among women who subsequently developed PE (511.5/430.8 ng/mL, P = 0.04). Finally, PlGF and sFlt-1 levels presented significantly different patterns between preeclamptic and normal pregnancies, being the strongest association in women with HP2-1 and HP2-2 phenotypes. Conclusion These findings suggest that HP phenotype could be useful in combination with first-trimester inflammatory and angiogenic markers to identify subsets of women with increased risk of PE development since early pregnancy.