MATERNAL-FETAL MEDICINE Elevated hyaluronan and extracellular matrix metalloproteinase inducer levels in women with preeclampsia Mariana Roma ˜o • Ingrid Cristina Weel • Shirlee Jaffe Lifshitz • Maria Terezinha Serra ˜o Perac ¸oli • Steven S. Witkin Received: 14 June 2013 / Accepted: 28 August 2013 / Published online: 11 September 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract Purpose Preeclampsia (PE) is a specific syndrome of pregnancy clinically identified by hypertension and pro- teinuria from the 20th week of gestation associated with a systemic inflammatory response and oxidative stress. While pro-inflammatory cytokines have been extensively studied in PE, other factors in the circulation that also influence the magnitude of inflammation have received much less attention. The present study compared serum concentrations of five immune-regulatory compounds in normotensive pregnant women and in women with gesta- tional hypertension (GH) or PE. Methods Sixty women with PE, 53 with GH and 40 normotensive women paired by gestational age were evaluated. Sera were evaluated for concentrations of extracellular matrix metalloproteinase inducer (EMM- PRIN), hyaluronan, gelsolin, visfatin and histone 2B by ELISA. Differences between groups were analyzed by nonparametric tests, with a significance level of 5 %. Results Increased levels of EMMPRIN and hyaluronan were present in preeclamptic women as compared to the GH and normotensive groups. There was no difference between groups in gelsolin, visfatin or histone 2B. Conclusion Increased release of EMMPRIN and hyalu- ronan may contribute to an elevated pro-inflammatory response and tissue damage in women with PE. Keywords Preeclampsia Á Gestational hypertension Á EMMPRIN Á Hyaluronan Á Inflammation Introduction Preeclampsia (PE) is a specific syndrome that affects a variable number of women, generally estimated to be between 2 and 8 % of pregnancies [1, 2]. It is a systemic disease clinically identified by hypertension and protein- uria in the second half of pregnancy [3, 4]. Although PE has no clearly defined etiology, several interacting mech- anisms appear to contribute to this multisystemic disease: inadequate placentation [5], endothelial dysfunction [6], immune maladaptation [7], oxidative stress [8–10] and an excessive pro-inflammatory response [11]. Pro-inflammatory cytokines have been exhaustively studied in PE and may play a role in the systemic inflam- matory response observed in this gestational pathology. However, other circulating factors that may influence the magnitude of inflammation have received less attention. The compounds measured in the present study also influ- ence the extent and duration of pro-inflammatory immunity and thereby can function as modulators of placental activity. Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a protein present on cell membranes and in the circulation. By inducing the release of matrix metalloproteinases EMMPRIN regulates the initiation and extent of tissue breakdown and M. Roma ˜o Á I. C. Weel Department of Gynecology and Obstetrics, Botucatu Medical School, Sa ˜o Paulo State University, Botucatu, Sa ˜o Paulo, SP, Brazil S. J. Lifshitz Á S. S. Witkin (&) Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Cornell Medical College, 525 East 68th Street, Box 35, New York, NY 10065, USA e-mail: switkin@med.cornell.edu M. T. S. Perac ¸oli Department of Microbiology and Immunology, Institute of Biosciences, Sa ˜o Paulo State University, Botucatu, SP, Brazil 123 Arch Gynecol Obstet (2014) 289:575–579 DOI 10.1007/s00404-013-3021-7