Search

Winkler et al raise an interesting point that perhaps lowering of soluble fms-like tyrosine kinase 1 (sFlt-1) may not have been the sole reason for the therapeutic benefit noted in our study,1 and that lowering other substances such as low-density lipoprotein cholesterol by dextran sulfate cellulose (DSC) apheresis may have contributed to the benefit we observed. In addition, Winkler et al contend that the therapeutic benefit noted in a prior study by Wang et al2 that used heparin-mediated extracorporeal low-density lipoprotein precipitation (HELP) apheresis may have been caused by lowering of low-density lipoprotein cholesterol. We agree with Winkler et al that we cannot conclude lowering sFlt-1 was the sole reason for the therapeutic benefit. Future clinical studies using specific apheretic columns (eg, sFlt-1 antibody columns) are needed to directly answer the contributing role of sFlt-1 in mediating preeclamptic signs and symptoms. We would like to point out that although lipid abnormalities frequently accompany …

Background— Targeted therapies to stabilize the clinical manifestations and prolong pregnancy in preeclampsia do not exist. Soluble fms-like tyrosine kinase 1 (sFlt-1), an alternatively spliced variant of the vascular endothelial growth factor receptor 1, induces a preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia. Removing sFlt-1 may benefit women with very preterm ( Methods and Results— We first show that negatively charged dextran sulfate cellulose columns adsorb sFlt-1 in vitro. In 5 women with very preterm preeclampsia and elevated circulating sFlt-1 levels, we next demonstrate that a single dextran sulfate cellulose apheresis treatment reduces circulating sFlt-1 levels in a dose-dependent fashion. Finally, we performed multiple apheresis treatments in 3 additional women with very preterm (gestational age at admission 28, 30, and 27+4 weeks) preeclampsia and elevated circulating sFlt-1 levels. Dextran sulfate apheresis lowered circulating sFlt-1, reduced proteinuria, and stabilized blood pressure without apparent adverse events to mother and fetus. Pregnancy lasted for 15 and 19 days in women treated twice and 23 days in a woman treated 4 times. In each, there was evidence of fetal growth. Conclusions— This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting.

The porcine lymphotropic herpesvirus 1 (PLHV-1), the first gammaherpesvirus of pigs, has been detected at a high prevalence in healthy pig populations. A porcine gammaherpesvirus has also been detected at high copy numbers in animals suffering from posttransplant lymphoproliferative disease (PTLD). While human PTLD is a EBV-associated complication following clinical transplantation, porcine PTLD is a disease recently described in pigs undergoing experimental allogeneic hematopoietic stem cell transplantation. Here we demonstrate that PLHV-1 and the virus present in porcine PTLD are indistinguishable, and present the characterization of 73 kbp of the genome of PLHV-1. We identified homologs of cellular genes, including a putative G protein-coupled receptor (GCR) as well as a viral homolog of the bcl-2 oncogene (v-bcl-2) and show significant transcription of these genes as well as of several other PLHV-1 genes in lymph nodes of a PTLD-affected pig. These data indicate that PLHV-1 is active during PTLD and may be involved in the etiology of this lymphoproliferative disease.