Annals of Hematology

, Volume 95, Issue 11, pp 1859–1867 | Cite as

Abnormal expression of inflammatory genes in placentas of women with sickle cell anemia and sickle hemoglobin C disease

  • Letícia C. Baptista
  • Maria Laura Costa
  • Regiane Ferreira
  • Dulcinéia M. Albuquerque
  • Carolina Lanaro
  • Kleber Y. Fertrin
  • Fernanda G. Surita
  • Mary A. Parpinelli
  • Fernando F. Costa
  • Mônica Barbosa de MeloEmail author
Original Article


Sickle cell disease (SCD) is a complex disease that is characterized by the polymerization of deoxyhemoglobin S, altered red blood cell membrane biology, endothelial activation, hemolysis, a procoagulant state, acute and chronic inflammation, and vaso-occlusion. Among the physiological changes that occur during pregnancy, oxygen is consumed by fetal growth, and pregnant women with SCD are more frequently exposed to low oxygen levels. This might lead to red blood cells sickling, and, consequently, to vaso-occlusion. The mechanisms by which SCD affects placental physiology are largely unknown, and chronic inflammation might be involved in this process. This study aimed to evaluate the gene expression profile of inflammatory response mediators in the placentas of pregnant women with sickle cell cell anemia (HbSS) and hemoglobinopathy SC (HbSC). Our results show differences in a number of these genes. For the HbSS group, when compared to the control group, the following genes showed differential expression: IL1RAP (2.76-fold), BCL6 (4.49-fold), CXCL10 (−2.12-fold), CXCR1 (−3.66-fold), and C3 (−2.0-fold). On the other hand, the HbSC group presented differential expressions of the following genes, when compared to the control group: IL1RAP (4.33-fold), CXCL1 (3.05-fold), BCL6 (4.13-fold), CXCL10 (−3.32-fold), C3 (−2.0-fold), and TLR3 (2.38-fold). Taken together, these data strongly suggest a differential expression of several inflammatory genes in both SCD (HbSS and HbSC), indicating that the placenta might become an environment with hypoxia, and increased inflammation, which could lead to improper placental development.


Sickle cell disease Placenta Pregnancy Inflammation Gene expression 



We thank Dr. Fred Kraus for helping with the morphology analysis of the H&E stained samples and Dr. Nicola Conran for the careful review of the manuscript.

This study was supported by São Paulo Research Foundation (FAPESP) grant 2008/57441-0, grant 2014/00984-3 and grant 2014/01925-0 to MLC and by the Coordination for the Improvement of Higher Education Personnel (CAPES) and the National Council for Scientific and Technological Development (CNPq).

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all patients for being included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2016_2780_MOESM1_ESM.docx (18 kb)
Supplementary Table 1 mRNA expression profile of PCR Array for Human Inflammatory Response & Autoimmunity of 84 genes in placentas of SCD groups. (DOCX 17 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Letícia C. Baptista
    • 1
  • Maria Laura Costa
    • 2
  • Regiane Ferreira
    • 3
  • Dulcinéia M. Albuquerque
    • 3
  • Carolina Lanaro
    • 3
  • Kleber Y. Fertrin
    • 3
  • Fernanda G. Surita
    • 2
  • Mary A. Parpinelli
    • 2
  • Fernando F. Costa
    • 3
  • Mônica Barbosa de Melo
    • 1
    • 4
    Email author
  1. 1.Center for Molecular Biology and Genetic Engineering (CBMEG)University of Campinas - UNICAMPCampinasBrazil
  2. 2.Department of Obstetrics and GynecologyUniversity of Campinas - UNICAMP, School of MedicineCampinasBrazil
  3. 3.Hematology and Hemotherapy CenterUniversity of Campinas - UNICAMPCampinasBrazil
  4. 4.Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering (CBMEG)University of Campinas - UNICAMPCampinasBrazil

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