Karen Priscilla Tezotto Pendeloski

Inflammatory Mediators Gene Polymorphisms in Preeclampsia

Objective. To assess a possible relation between proinflammatory mediators (IL-1R1, IL-12, IL-18, TLR-2, and TLR-4) gene polymorphisms and preeclampsia (PE). Methods. Genotyping was performed on 109 preeclamptic patients and 174 healthy fertile women with at least two previous successful pregnancies (controls). χ2 or Fishers exact test were used to compare genotype frequencies. The control group included 174 pregnant women matched by race to the study group. Results. Genotypic and allelic distributions for all six polymorphisms were similar between the study and control groups. IL-1R1 (PstI, rs2234650): p = 0.82 ; IL-12 (+1188, rs3212227): p = 0.93; IL-18 (−137, rs187238): p = 0.74 ; IL-18 (−607, rs1946519): p = 0.22; TLR-2 (+2258, rs5743708): p = 0.97; and TLR-4 (+896, rs4986790): p = 0.23. Conclusion. The analyzed gene polymorphisms are not associated with PE.

Maternal obesity and inflammatory mediators: A controversial association

The link between maternal obesity and inflammatory mediators is still unclear. Our aim was to summarize the main findings of recently published studies on this topic. We performed a search in Medline for studies published in the last years on obesity, human pregnancy, and inflammatory mediators. We report the findings of 30 studies. The characteristics and number of participants, study design, gestational age at sample collection, and type of sample varied widely. Approximately two‐thirds of them investigated more than one mediator, and 50% included participants in only one trimester of pregnancy. The most frequently investigated mediators were leptin, tumour necrosis factor‐alpha (TNF‐α), and interleukin (IL)‐6. Almost all studies reported an association between maternal obesity, leptin, and C‐reactive protein (CRP) serum levels but not with IL‐1β and IL‐10. The association of IL‐6, TNF‐α, monocyte chemo‐attractant protein‐1 (MCP‐1), adiponectin, and resistin with maternal obesity is still controversial. To clarify the physiopathological link between maternal obesity and inflammation, more high‐quality studies are needed.

Angiogenic factors and uterine Doppler velocimetry in early- and late-onset preeclampsia

To assess correlations between maternal serum levels of pro‐ and anti‐angiogenic factors with uterine perfusion in women with early‐ compared with late‐onset preeclampsia, and in healthy pregnant women.

Immunoregulatory molecules in patients with gestational diabetes mellitus

Induction of maternal-fetal immune tolerance is essential for the development of normal pregnancy. Impaired expression of costimulatory molecules may lead to intense inflammatory reaction, a mechanism involved in the pathophysiology of gestational diabetes mellitus (GDM). The aim of this study was to investigate whether immunoregulatory molecules are involved in the physiopathology of GDM. This case–control study included 30 healthy pregnant women and 20 GDM patients. Flow cytometry was used to assess peripheral blood T subpopulations (CD4+ and CD8+), the expression of immunoregulatory molecules (CD28, ICOS, CTLA-4, and PD-1) and activation markers (CD69 and HLA-DR). Compared to healthy women, GDM patients had a significantly higher frequency of CD4+CD69+ and CD8+CD69+ T cells; only patients with insulin-treated GDM had increased numbers of CD4+HLA-DR+ T cells. We also observed significantly higher percentages of CD4+CD28+HLA-DR+, CD3+CD4+ICOS+, CD3+CD4+PD-1+, CD8+CD28+CD69+, CD8+CD28+HLA-DR+, CD8+CTLA-4+HLA-DR+, and CD3+CD8+ICOS+ T cells and lower frequency of CD3+CD4+CTLA-4+, CD3+CD8+CTLA-4+, and CD8+ICOS+HLA-DR+ T cells in GDM patients compared to healthy pregnant women. This first study assessing costimulatory molecules in GDM patients shows that these patients have exacerbated markers of T cell activation along with CTLA-4 deficiency, findings that indicate that the maternal-fetal tolerance is compromised in these patients.

Immunoregulatory gene polymorphisms in women with preeclampsia

The costimulatory molecules CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4) (cytotoxic T-lymphocyte-associated antigen-4) and inducible costimulator (ICOS) are believed to have a critical modulatory role in the immune response. However, few studies have been performed on the role of these immune regulatory molecules and their polymorphisms in women with preeclampsia (PE). The aim of our study was to evaluate the CTLA4 (+49 A/G) (rs 231775), CD28 (+17 T/C) (rs 3116496) and ICOS (−1564 T/C) (rs 4675378) gene polymorphisms in Brazilian women with PE. This case–control study included 130 patients with PE and 261 control women without any obstetric or systemic disorders. Genomic DNA was extracted from peripheral blood, and the polymorphism genotyping was performed by digesting the PCR products with the restriction endonucleases BbvI (CTLA-4), AfeI (CD28) and AluI (ICOS). Data were analyzed by χ2 or Fishers exact test; a P-value of <0.05 was considered as significant. There were significant differences in the ICOS genotype and allelic frequencies between the PE and control groups (P=0.01 and P=0.01, respectively). We found a significantly lower frequency of the ICOS (−1564) T allele in women with mild PE compared with the controls. There were no differences in the CTLA-4 (+49 A/G) and CD28 (+17 T/C) genotypes and allelic frequencies between the PE patients and controls. Our data suggest that PE is associated with ICOS, but is not associated with the CTLA-4 or CD28 gene polymorphisms.

FAS and FAS-L genotype and expression in patients with recurrent pregnancy loss.

We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case–control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules.

Impaired Treg and NK cells profile in overweight women with gestational diabetes mellitus

Maternal obesity is frequently associated with gestational diabetes mellitus (GDM), and immunological mechanisms seem to be involved in the physiopathology of these conditions. The aim of this study was to characterize the profile of immune cells in peripheral blood of overweight women with GDM.

ORIGINAL ARTICLE: Association Study of Vascular Endothelial Growth Factor and Polymorphisms of its Gene with Ectopic Pregnancy

Citation Elito J Jr, Daher S, Fernandes da Silva MO, Marconi NMH, Pendeloski KPT, Moron AF, Camano L. Association study of vascular endothelial growth factor and polymorphisms of its gene with ectopic pregnancy. Am J Reprod Immunol 2010; 63: 120–125

ORIGINAL ARTICLE: Association Study of Vascular Endothelial Growth Factor and Polymorphisms of its Gene with Ectopic Pregnancy: VEGF POLYMORPHISM WITH ECTOPIC PREGNANCY

Citation Elito J Jr, Daher S, Fernandes da Silva MO, Marconi NMH, Pendeloski KPT, Moron AF, Camano L. Association study of vascular endothelial growth factor and polymorphisms of its gene with ectopic pregnancy. Am J Reprod Immunol 2010; 63: 120–125