{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:37:07Z","timestamp":1793299027273,"version":"4.5.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2008,4,2]],"date-time":"2008-04-02T00:00:00Z","timestamp":1207094400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0001865","type":"journal-article","created":{"date-parts":[[2008,4,1]],"date-time":"2008-04-01T20:30:36Z","timestamp":1207081836000},"page":"e1865","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":73,"title":["Maternal TLR4 and NOD2 Gene Variants, Pro-Inflammatory Phenotype and Susceptibility to Early-Onset Preeclampsia and HELLP Syndrome"],"prefix":"10.1371","volume":"3","author":[{"given":"Bas B.","family":"van Rijn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Franx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A. P.","family":"Steegers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christianne J. M.","family":"de Groot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier M.","family":"Bertina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Pasterkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hieronymus A. M.","family":"Voorbij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hein W.","family":"Bruinse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Roest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2008,4,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1126\/science.1111726","article-title":"Latest advances in understanding preeclampsia.","volume":"308","author":"CW Redman","year":"2005","journal-title":"Science"},{"key":"ref2","article-title":"Make Every Mother and Child Count.","year":"2005"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.siny.2006.04.001","article-title":"Inflammation and pre-eclampsia.","volume":"11","author":"AM Borzychowski","year":"2006","journal-title":"Semin Fetal Neonatal Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1097\/00007611-200008000-00005","article-title":"Leukocytosis is proportional to HELLP syndrome severity: evidence for an inflammatory form of preeclampsia.","volume":"93","author":"DA Terrone","year":"2000","journal-title":"South Med J"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/j.1749-6632.1994.tb21740.x","article-title":"Human trophoblast invasion. Autocrine control and paracrine modulation.","volume":"734","author":"MT McMaster","year":"1994","journal-title":"Ann N Y Acad Sci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1046\/j.1523-1755.1998.00097.x","article-title":"Nature of glomerular dysfunction in pre-eclampsia.","volume":"54","author":"RA Lafayette","year":"1998","journal-title":"Kidney Int"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/01.ogx.0000256779.06275.c4","article-title":"Inflammatory changes in preeclampsia: current understanding of the maternal innate and adaptive immune response.","volume":"62","author":"N Visser","year":"2007","journal-title":"Obstet Gynecol Surv"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1146\/annurev.immunol.22.012703.104622","article-title":"Interleukin-10 and related cytokines and receptors.","volume":"22","author":"S Pestka","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1097\/00003246-200107001-00002","article-title":"Sepsis and evolution of the innate immune response.","volume":"29","author":"B Beutler","year":"2001","journal-title":"Crit Care Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/01.all.0000200503.77295.bb","article-title":"The role of Toll-like receptors and related receptors of the innate immune system in asthma.","volume":"6","author":"IA Yang","year":"2006","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1016\/S0140-6736(00)05091-1","article-title":"Crohn's disease: genetic susceptibility, bacteria, and innate immunity.","volume":"357","author":"DA Van Heel","year":"2001","journal-title":"Lancet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/0002-9378(94)90463-4","article-title":"A new animal model for human preeclampsia: ultra-low-dose endotoxin infusion in pregnant rats.","volume":"171","author":"MM Faas","year":"1994","journal-title":"Am J Obstet Gynecol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/76048","article-title":"TLR4 mutations are associated with endotoxin hyporesponsiveness in humans.","volume":"25","author":"NC Arbour","year":"2000","journal-title":"Nat Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/S0140-6736(06)68345-1","article-title":"New genes in inflammatory bowel disease: lessons for complex diseases?","volume":"367","author":"DR Gaya","year":"2006","journal-title":"Lancet"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/35079107","article-title":"Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.","volume":"411","author":"JP Hugot","year":"2001","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1097\/01.gim.0000187223.69947.db","article-title":"Genetic variation associated with preterm birth: a HuGE review.","volume":"7","author":"KS Crider","year":"2005","journal-title":"Genet Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1056\/NEJMoa012673","article-title":"Toll-like receptor 4 polymorphisms and atherogenesis.","volume":"347","author":"S Kiechl","year":"2002","journal-title":"N Engl J Med"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1053\/plac.2001.0785","article-title":"Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia.","volume":"23","author":"JM Sikkema","year":"2002","journal-title":"Placenta"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ajog.2006.06.044","article-title":"Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia.","volume":"195","author":"BB van Rijn","year":"2006","journal-title":"Am J Obstet Gynecol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/S0002-9378(99)70335-2","article-title":"Preeclampsia and genetic risk factors for thrombosis: a case-control study.","volume":"181","author":"CJ De Groot","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"IX","DOI":"10.3109\/10641950109152635","article-title":"The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP).","volume":"20","author":"MA Brown","year":"2001","journal-title":"Hypertens Pregnancy"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/0002-9378(86)90266-8","article-title":"Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia.","volume":"155","author":"BM Sibai","year":"1986","journal-title":"Am J Obstet Gynecol"},{"key":"ref23","first-page":"349","article-title":"[Intrauterine growth and intrauterine growth curves].","volume":"69","author":"GJ Kloosterman","year":"1969","journal-title":"Ned Tijdschr Verloskd Gynaecol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jim.2004.03.013","article-title":"Single step high-throughput determination of Toll-like receptor 4 polymorphisms.","volume":"289","author":"BB van Rijn","year":"2004","journal-title":"J Immunol Methods"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1111\/j.1538-7836.2006.02205.x","article-title":"Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.","volume":"4","author":"JJ Hulstein","year":"2006","journal-title":"J Thromb Haemost"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1001\/jama.286.2.180","article-title":"Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.","volume":"286","author":"RB D'Agostino Sr.","year":"2001","journal-title":"Jama"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1161\/01.HYP.0000143849.67254.ca","article-title":"Short- and long-term changes in plasma inflammatory markers associated with preeclampsia.","volume":"44","author":"DJ Freeman","year":"2004","journal-title":"Hypertension"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1146\/annurev.immunol.24.021605.090552","article-title":"Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large.","volume":"24","author":"B Beutler","year":"2006","journal-title":"Annu Rev Immunol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.4049\/jimmunol.168.3.1435","article-title":"Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway.","volume":"168","author":"Y Bulut","year":"2002","journal-title":"J Immunol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/80833","article-title":"Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus.","volume":"1","author":"EA Kurt-Jones","year":"2000","journal-title":"Nat Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"8606","DOI":"10.1074\/jbc.M413541200","article-title":"Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity.","volume":"280","author":"G Krishnegowda","year":"2005","journal-title":"J Biol Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4049\/jimmunol.177.1.322","article-title":"Analysis of TLR4 polymorphic variants: new insights into TLR4\/MD-2\/CD14 stoichiometry, structure, and signaling.","volume":"177","author":"P Rallabhandi","year":"2006","journal-title":"J Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1073\/pnas.0506803102","article-title":"Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria.","volume":"103","author":"FP Mockenhaupt","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref34","first-page":"227","article-title":"Maternal periodontal disease is associated with an increased risk for preeclampsia.","volume":"101","author":"KA Boggess","year":"2003","journal-title":"Obstet Gynecol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.2353\/ajpath.2006.050781","article-title":"Adeno-associated virus-2 (AAV-2) causes trophoblast dysfunction, and placental AAV-2 infection is associated with preeclampsia.","volume":"168","author":"F Arechavaleta-Velasco","year":"2006","journal-title":"Am J Pathol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1056\/NEJMc052721","article-title":"Elevated sFlt1 level and preeclampsia with parvovirus-induced hydrops.","volume":"354","author":"H Stepan","year":"2006","journal-title":"N Engl J Med"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/j.1471-0528.2003.02481.x","article-title":"Levels of antibodies against cytomegalovirus and Chlamydophila pneumoniae are increased in early onset pre-eclampsia.","volume":"110","author":"P von Dadelszen","year":"2003","journal-title":"Bjog"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1471-0528.2004.00423.x","article-title":"Association of raised titres of antibodies to Chlamydia pneumoniae with a history of pre-eclampsia.","volume":"112","author":"DG Goulis","year":"2005","journal-title":"Bjog"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1086\/505152","article-title":"Common polymorphisms of toll-like receptors 4 and 9 are associated with the clinical manifestation of malaria during pregnancy.","volume":"194","author":"FP Mockenhaupt","year":"2006","journal-title":"J Infect Dis"},{"key":"ref40","first-page":"459","article-title":"Effect of the HELLP syndrome on maternal immune function.","volume":"38","author":"DS Cunningham","year":"1993","journal-title":"J Reprod Med"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/0002-9378(91)91429-Z","article-title":"The natural history of HELLP syndrome: patterns of disease progression and regression.","volume":"164","author":"JN Martin Jr.","year":"1991","journal-title":"Am J Obstet Gynecol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ejogrb.2005.11.041","article-title":"A randomised placebo-controlled trial of prolonged prednisolone administration to patients with HELLP syndrome remote from term.","volume":"128","author":"PJ van Runnard Heimel","year":"2006","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4049\/jimmunol.164.2.558","article-title":"Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex.","volume":"164","author":"K Ohashi","year":"2000","journal-title":"J Immunol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"10229","DOI":"10.1074\/jbc.M100099200","article-title":"The extra domain A of fibronectin activates Toll-like receptor 4.","volume":"276","author":"Y Okamura","year":"2001","journal-title":"J Biol Chem"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.1071059","article-title":"The danger model: a renewed sense of self.","volume":"296","author":"P Matzinger","year":"2002","journal-title":"Science"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.ajog.2003.12.019","article-title":"Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia.","volume":"190","author":"RJ Levine","year":"2004","journal-title":"Am J Obstet Gynecol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1056\/NEJMoa031884","article-title":"Circulating angiogenic factors and the risk of preeclampsia.","volume":"350","author":"RJ Levine","year":"2004","journal-title":"N Engl J Med"},{"key":"ref48","first-page":"921","article-title":"Toll-like receptor 4: a potential link between \u201cdanger signals,\u201d the innate immune system, and preeclampsia?","volume":"193","author":"YM Kim","year":"2005","journal-title":"Am J Obstet Gynecol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/ni1092","article-title":"NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses.","volume":"5","author":"T Watanabe","year":"2004","journal-title":"Nat Immunol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1600-0897.2006.00447.x","article-title":"NOD protein expression and function in first trimester trophoblast cells.","volume":"57","author":"MJ Costello","year":"2007","journal-title":"Am J Reprod Immunol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000097926","article-title":"Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes.","volume":"63","author":"KA Goddard","year":"2007","journal-title":"Hum Hered"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"IV6","DOI":"10.1161\/01.CIR.0000133444.17867.56","article-title":"Established and emerging plasma biomarkers in the prediction of first atherothrombotic events.","volume":"109","author":"PM Ridker","year":"2004","journal-title":"Circulation"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/S0140-6736(00)05112-6","article-title":"Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births.","volume":"357","author":"GC Smith","year":"2001","journal-title":"Lancet"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0140-6736(05)67424-7","article-title":"Genetic association studies.","volume":"366","author":"HJ Cordell","year":"2005","journal-title":"Lancet"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0001865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T09:55:56Z","timestamp":1708768556000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0001865"}},"subtitle":[],"editor":[{"given":"Henry","family":"Harpending","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2008,4,2]]},"references-count":54,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2008,4,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0001865","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,2]]}}}