No abstract

Preeclampsia is a major cause of morbidity and mortality during pregnancy. To date, the pathogenesis of the disease is not fully understood. Recent studies show that preeclampsia is associated with overexpression of hemoglobin genes α2 and γ and accumulation of the protein in the vascular lumen of the placenta. Hypothesizing that cell-free hemoglobin leaks from the placenta into the maternal circulation and contributes to the endothelial damage and symptoms by inducing oxidative stress, we analysed fetal and adult hemoglobin (HbF, HbA), haptoglobin, oxidation markers and the heme scavenger and antioxidant α 1 -microglobulin in plasma, urine and placenta in preeclamptic women (n=28) and normal pregnancies (n=27).The mean plasma concentrations of HbF, HbA, protein carbonyl groups, membrane peroxidation capacity and α 1 -microglobulin were significantly increased in preeclamptic women. The levels of total plasma Hb correlated strongly with the systolic blood pressure.The plasma haptoglobin concentrations of women with preeclampsia were significantly depressed. Increased amounts of α 1 -microglobulin-mRNA and protein were found in placenta from preeclamptic women and the levels of plasma and placenta α 1 -microglobulin correlated to plasma Hb-concentrations. The heme-degrading form t-α 1 -microglobulin was significantly increased in urine in preeclampsia. These results support that hemoglobin-induced oxidative stress is a pathogenic factor in preeclampsia.

BACKGROUND:  In the ABO blood group system mutations in the A gene may lead to weak A subgroups owing to a dysfunctional 3‐α‐N‐acetylgalactosaminyltransferase. STUDY DESIGN AND METHODS:  Blood and DNA were investigated to correlate weak A phenotypes with genotype, and an overrepresentation of the infrequent O2 allele was observed. Consequently, 57 available O2 alleles were examined in detail. RESULTS:  Two new O2 alleles were identified having mutations resulting in Gly229Asp with or without Arg217Cys. A recently described O2 variant (488C>T; Thr163Met) was also found. Surprisingly, both the original and the variant O2 alleles were associated with either O or Aweak phenotypes. Three novel O alleles surfaced in six other samples with suspected A subgroups. These were A1‐like alleles having nonsense mutations causing premature truncation at codons 56, 107, or 181. A second example of the rare O3 allele was also identified. A newly described O1 allele having 768C>A was found to be the third most frequent O allele among Swedish donors. Of the five novel O alleles, three were incorrectly interpreted as A1 following routine ABO genotyping. CONCLUSION:  Apparent O alleles lacking 261delG may cause weak A expression on red blood cells and/or inhibit anti‐A production. A hypothesis that exchange of genetic material between principally dissimilar O alleles during mitosis (“autologous chimerism”) restores glycosyltransferase activity in some cells would explain this interesting phenomenon.