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CD4+ regulatory T lymphocytes in preeclamptic women and in their newborns: preliminary results.

David F. Navarro Barquín1, 2, Leonel Daza Benítez2*, Sergio Lopez Briones3, Ana Laura Macías Rocha4 and Alma Patricia González5
  • 1 University Of Guanajuato, Department of Medicine and Nutrition, Mexico
  • 2 High Specialty Medicine Unit Number 48, Mexican Institut of Social Security, Research Division, Mexico
  • 3 University of Guanjuato, Deparment of Medical Sciences, Mexico
  • 4 High Specialty Medicine Unit Number 48, Mexican Institut of Social Security, Gynecology Division, Mexico
  • 5 High Specialty Medicine Unit Number 48, Mexican Institut of Social Security, Neonatal Division, Mexico

Introduction:
Preeclampsia is one of the most important cause of mortality and morbility in pregnancy worldwide right below obstetric hemorrhage and in Mexico it takes the first place in maternal dead, also is consider the first cause of preterm birth associated to maternal cause. 1-2
One of the bigger challenges in these pathology is that the pathogenic mechanism is still unknown, at the moment there are only hypothesis about it and one of the most important is that a immunological mechanism is involve in their genesis.
This hypothesis is supported primarily by epidemiological studies where it was associated with the first pregnancy, short sexual cohabitation period, diminished exposition to sperm (assisted reproduction technics) and change of paternity in secondary pregnancies. 3-6
The pathogenesis of the immunological mechanism is study by different angles one is the diminish of the population of the Tregs cells (CD4+CD25+FOXP3+) that are documented that they increase during healthy pregnancy 7, and first studied their decrease in the decidua and in peripheral blood at the third trimester and documented the decrease of these population 8. Nevertheless there are also some authors that haven’t found these alterations, that is why the role of this population is still uncertain. 9
The immune profile of the newborn is still in study, and is basically affected by the gestational age of the newborn, but certain parameters are already established and their proportion in the umbilical cord blood 10. However we search in the pubmed database information about references of if there is alteration in the newborns of mothers with this pathology.

Objective:
Our aim was to study the proportion of regulatory T cells in preeclamptic women and in their newborns.

Methods:
The CD4+CD25+high FOXP3+, CD3+, CD4+, CD8+, CD20+, TCR gamma-delta, CD69+ surface markers and hormone profile were measured in 23 women with preeclampsia (PE) and in 14 of their newborns the T-reg, CD3+, CD4+, CD8+, CD20+, TCR gamma-delta, CD69+ surface markers were measured also the Fenton prescriptive growth charts for classifying into intrauterine growth-restricted and small for gestational age infants were applied. Fourteen healthy women paired by age and pregnancy number (HC) and 5 newborns paired by gestational age were included as controls. To measure the cell surface markers was use a FAC scan canto II ®, software: BD FACSDiva 6.1.3 Beckton Dickinson. The statistical analysis used was t student for the parametric variables and logistic regression in SPSS 15.

Results:
The T-regs cells proportion was 2.93% in PE and vs. 5.54% in HC (p = 0.031). The CD4+CD25+high cells were in PE 3.71% vs. HC 7.41% in HC, (p= 0.020); Total IgG level was 847mg/dl in PE vs. 955 mg/dl in HC (p= 0.117). In the umbilical cord blood samples we found 4.56% in T regs cells in PE vs.8.54% in HC (p = 0.201). While gamma-delta T-cells were 3.61 in PE vs. 20.87% in HC, (p= 0.063). Interestingly, CD4+CD69+ cells were 10.03% in PE and 28.22% in HC (p=0.190).

Conclusions:
We found decreased proportion of T-regs cells in preeclamptic women as previously have been reported by other authors. Also we observed a tendency of decreasing levels of IgG in women with PE, in relation to the hypothesis of the increased of immunologic response mediated by T cells. Regarding, hormone profiles we found no statistical significance. In the newborns we found a tendency of decreased T-regs cells, gamma-delta T cells, and a low expression of CD69 on CD4 cells, an important early activation marker expressed by lymphocytes. Nevertheless, the number of patients included in this study is still small, but we can suggest that PE has a repercussion in the immunological cell profile of their newborns, and it could be an explanation for the increased morbility and mortality in the newborns.

References

1. Roberts JM, Pearson GD, Cutler JA, Lindheimer MD;National Heart Lung and Blood Institute. Summary of the NHLBI working group on research on hypertension during pregnancy, Hypertension. (2003) 41:437-45
2. COMEGO. Guía de Práctica Clínica. Diagnóstico y tratamiento de la preeclampsia-eclampsia. Ginecol Obstet Mex (2010) 78:S461-S525
3. Robillard PY, Hulsey TC, Perianin J, Janky E, Miri EH, Papiernik E. Association of pregnancy-induced hypertension with duration of sexual cohabitation before conception. Lancet (1994) 344:973–75.
4. Robillard PY, Hulsey TC, Alexander GR, Keenan A, de Caunes F, Papiernik E. Paternity patterns and risk of preeclampsia in the last pregnancy in multiparae. J Reprod Immunol (1993) 24:1–12.
5. Trupinls, Simonlp, Eskenazi B. Change in paternity: a risk factor for preeclampsia in multiparas. Epidemiology (1996) 7:2–244.
6. Salomon CG, Seely EW. Preeclampsia-serching for the cause. N Engl J Med (2004) 350:641-642.
7. Tilburgs T, Roelen DL, Van Der Mast BJ, de Groot-Swings GM, Kleijburg C, Scherjon SA, Claas FH. Evidence for a selective migration of fetus-specific cd4+ cd25+ bright regulatory t cells from peripheral blood to the decidua in human pregnancy. J Immunol (2008) 180:5737-5745
8. Sasaki Y , Darmochwal-Kolarz D, Suzuki D, Sakai M, Ito M, Shima T, Shiozaki A, Rolinski J, Saito S. et al. Proportion of peripheral blood and decidual cd4+ cd25bright regulatory t cells in pre-eclampsia, Clinical And Experimental Immunology, (2007) 149: 139–145
9. Paeschke S, Chen F, Horn N, Fotopoulou C, Zambon-Bertoja A, Sollwedel A, Zenclussen ML, Cassalis PA, Dudenhausen JW, Volk HD, Zenclussen AC. Pre-eclampsia is not associated with changues in the levels of regulatory T cells in periphereal blood. Am J Reprod Immunol (2005) 54: 384-89)
10. Kim H, Moon HW, Hur M, Park CM, Yun YM, Hwang HS, Kwon HS, Sohn IS. Distribution of CD4+ CD25+ high FoxP3 + regulatory T-cell in umbilical cord blood. Pediatr Res (2012) 5:590-7

Keywords: T regulatory cells, Preeclampsia, newborns, Labor, Obstetric, Mexico

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Immune-mediated disease pathogenesis

Citation: Navarro Barquín DF, Daza Benítez L, Lopez Briones S, Macías Rocha A and González A (2013). CD4+ regulatory T lymphocytes in preeclamptic women and in their newborns: preliminary results.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01166

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Received: 31 Jul 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Leonel Daza Benítez, High Specialty Medicine Unit Number 48, Mexican Institut of Social Security, Research Division, León, Guanajuato, 37320, Mexico, leonel.daza@imss.gob.mx