Introduction: The analysis of cell-free DNA from maternal blood samples has facilitated the noninvasive detection of fetal aneuploidies or hereditary Mendelian disorders. In this context, previous studies have indicated that the pool of cell-free DNA is greater in maternal serum than in plasma samples, necessitating optimized collection and storage protocols. As the source of this increased amount of cell-free DNA is not clear, we have now examined whether neutrophil extracellular traps (NETs) contribute to this material. Material and Methods: Serum samples were collected in all three trimesters of normal healthy pregnant women, and at term from cases with manifest preeclampsia. The presence of NET-derived material was demonstrated by the detection of cell-free DNA fragments complexed to neutrophil granular proteins (i.e. myeloperoxidase). Results: Our data indicate that NET-derived cell-free DNA/myeloperoxidase complexes were greater in serum from normal pregnant women than in normal matching nonpregnant controls. This neutrophil chromosomal material increased incrementally throughout gestation and was most pronounced in cases with preeclampsia. Discussion: By detecting increased levels of cell-free DNA/myeloperoxidase complexes in maternal serum samples, our data indicate that a significant proportion of this material is derived from the generation of NETs.

1.
Lo YM: Noninvasive prenatal diagnosis: from dream to reality. Clin Chem 2015;61:32-37.
2.
Barrett AN, Zimmermann BG, Wang D, Holloway A, Chitty LS: Implementing prenatal diagnosis based on cell-free fetal DNA: accurate identification of factors affecting fetal DNA yield. PLoS One 2011;6:e25202.
3.
Buysse K, Beulen L, Gomes I, et al: Reliable noninvasive prenatal testing by massively parallel sequencing of circulating cell-free DNA from maternal plasma processed up to 24 h after venipuncture. Clin Biochem 2013;46:1783-1786.
4.
Wong D, Moturi S, Angkachatchai V, et al: Optimizing blood collection, transport and storage conditions for cell free DNA increases access to prenatal testing. Clin Biochem 2013;46:1099-1104.
5.
Lo YM, Tein MS, Lau TK, et al: Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998;62:768-775.
6.
Lo YM, Leung TN, Tein MS, et al: Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia. Clin Chem 1999;45:184-188.
7.
Zhong XY, Holzgreve W, Hahn S: Circulatory fetal and maternal DNA in pregnancies at risk and those affected by preeclampsia. Ann N Y Acad Sci 2001;945:138-140.
8.
Brinkmann V, Reichard U, Goosmann C, et al: Neutrophil extracellular traps kill bacteria. Science 2004;303:1532-1535.
9.
Kessenbrock K, Krumbholz M, Schonermarck U, et al: Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 2009;15:623-625.
10.
Gupta AK, Hasler P, Holzgreve W, Gebhardt S, Hahn S: Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia. Hum Immunol 2005;66:1146-1154.
11.
Sur Chowdhury C, Giaglis S, Walker UA, Buser A, Hahn S, Hasler P: Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis Res Ther 2014;16:R122.
12.
Zhong XY, Laivuori H, Livingston JC, et al: Elevation of both maternal and fetal extracellular circulating deoxyribonucleic acid concentrations in the plasma of pregnant women with preeclampsia. Am J Obstet Gynecol 2001;184:414-419.
13.
Zhong XY, von Muhlenen I, Li Y, et al: Increased concentrations of antibody-bound circulatory cell-free DNA in rheumatoid arthritis. Clin Chem 2007;53:1609-1614.
14.
Gupta AK, Hasler P, Holzgreve W, Hahn S: Neutrophil NETs: a novel contributor to preeclampsia-associated placental hypoxia? Semin Immunopathol 2007;29:163-167.
15.
Zhong XY, Wang Y, Chen S, et al: Circulating fetal DNA in maternal plasma is increased in pregnancies at high altitude and is further enhanced by preeclampsia. Clin Chem 2004;50:2403-2405.
16.
Redman CW, Sacks GP, Sargent IL: Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol 1999;180:499-506.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.