Functional evaluation of immunoregulatory molecules HLA-G, galectin-1, and IL-10 in people living with HIV.

OBJECTIVES: Investigate polymorphisms and expressions of human leukocyte antigen-G (HLA-G), galectin-1 (Gal-1), and interleukin-10 (IL-10) in people living with HIV (PLHIV) with and without comorbidities to help understanding the mechanisms involved in triggering these disorders in PLHIV and in their prognosis. DESIGN: Here we evaluated the potential correlation between the genetic polymorphism and/or protein levels of HLA-G, Gal-1, and IL-10 with and without comorbidities of PLHIV. METHODS: Two hundred HIV patients under antiretroviral treatment (83 with comorbidities and 117 without comorbidities) and 200 healthy individuals (controls) were genotyped, using PCR, for HLA-G 14-base pair polymorphism located at the 3' untranslated region in exon 8 insertion/insertion (Ins/Ins: low HLA-G expression) or deletion/deletion (Del/Del: high HLA-G expression). Soluble levels of HLA-G (sHLA-G), Gal-1, and IL-10 were quantified by enzyme-linked immunosorbet assay. RESULTS: HIV patients without comorbidities exhibited higher frequency of 14-base pair Del/Del genotype than HIV patients with comorbidities. As expected, HIV patients Ins/Ins with and without comorbidities produced less sHLA-G than controls. However, HIV patients Del/Del with comorbidities expressed sHLA-G more than controls and HIV patients Del/Del without comorbidities. Interestingly, patients that showed low levels sHLA-G, and presence of comorbidities, exhibited high Gal-1 serum levels. However, an increase in soluble levels of IL-10 in PLHIV was observed when compared to controls, especially in the PLHIV group without comorbidities suggesting, a protective role of IL-10 in the development of comorbidities. CONCLUSIONS: These data suggested that the high expression of sHLA-G and IL-10 or Gal-1 could be associated and could be associated with the development or not of comorbidities in PLHIV.

Interaction between oral estrogen plus progestogen therapy and ABO blood groups on coagulation activation in postmenopausal women.

OBJECTIVE: The aim of this study was to investigate the effect of postmenopausal hormone therapy on coagulation and whether this effect differs according to ABO blood groups. METHODS: This was a prospective observational study to evaluate factor VIII (FVIII) activity, factor von Willebrand (vWF), and D-dimer (D-Di) levels and ABO blood groups in 61 postmenopausal women using oral estrogen plus progestogen therapy (EPT; 2 mg estradiol + 1 mg norethisterone acetate) for 3 months and in 101 women not using EPT. After 3 months, all eligible women who had completed the treatment scheme proposed for the EPT group or those who opted to participate but had not undergone EPT had a blood sample collected for analysis. RESULTS: Significant differences were observed in FVIII activity and vWF levels in the control group between those carrying group O and non-group O blood. For EPT users, significant differences were observed for FVIII activity, vWF, and D-Di levels. After a multivariate regression analysis, FVIII activity and ABO blood groups were independently associated with vWF levels, whereas interaction between ABO blood groups and EPT were independently associated with FVIII activity. Besides diabetes, the ABO × EPT interaction was also noted to be independently associated with D-Di levels. CONCLUSIONS: These findings suggest an interactive effect between oral EPT and non-O blood groups, contributing to the mechanism by which estrogen triggers the hypercoagulability state and increased risk for venous thrombosis in women undergoing oral EPT.

Assessment of hypercoagulability markers and lipid levels in postmenopausal women undergoing either oral or transdermal hormone replacement therapy.

BACKGROUND: This study investigated the effect of either oral or transdermal hormone replacement therapy (HRT) on haemostatic, fibrinolytic and lipid profiles in a group of Brazilian women 3 months after beginning treatment by comparing these results with those obtained immediately before HRT. METHODS: Plasma levels of TAT, DDi, F1+2, PC, PS, AT, PAI-1 and serum lipids were determined in blood samples collected from 24 women undergoing oral HRT and from 11 women undergoing transdermal HRT. RESULTS: Significant increases in DDi and F1+2 plasma levels were observed after 3 months of oral HRT, while PS levels decreased. After transdermal HRT, a significant decrease was observed only for AT levels. CONCLUSION: After 3 months of oral HRT and in the absence of major genetic and acquired risk factors, women displayed a predisposition for activation of blood coagulation, and an increased activity of the fibrinolytic system. Oral HRT seemed to be more effective in predisposing haemostatic changes as compared to transdermal.

Increased Factor V Leiden frequency is associated with venous thrombotic events among young Brazilian patients.

INTRODUCTION: Of the inherited thrombophilias, the Factor V Leiden (FVL) and the prothrombin mutant (FII G20210A) are associated with increased risk of venous thromboembolism (VTE). The C677T mutation of the methylenetetrahydrofolate reductase gene, which may lead to hyperhomocysteinemia, is also considered a risk factor for VTE in some studies. However, the frequency of these genetic risk factors may vary significantly among different populations. MATERIAL AND METHODS: The FVL, FII G20210A and C677T mutations were investigated by PCR-RFLP in 275 young VTE Brazilian patients as well as in 324 biologically unrelated individuals selected to compose the control group. RESULTS: The C677T mutation in the MTHFR gene was detected in 135 (49.1%) patients, of which 117 (42.5%) were identified as heterozygous and 18 (6.5%) as homozygous. The G20210A mutation was detected in 14 (5.1%) patients in heterozygosis. In both cases, no significant difference was observed when these results were compared to the frequencies observed in the control group. FVL was detected in heterozygosis in 19 (6.9%) patients, corresponding to a significantly increased frequency when compared to that observed for the control group (1.2%) (OR 5.9; 95% CI 2.08-16.79; p < 0.001). CONCLUSIONS: The data indicated that FVL is significantly associated with VTE among young Brazilian patients, but also supported previous evidence that VTE is a multi-factorial disease, resulting from the interaction of genetic and acquired risk factors.

Inherited thrombophilias and pre-eclampsia in Brazilian women.

OBJECTIVE: The aim of the present study was to compare the distribution of G1691A, G20210A and C677T mutations in pre-eclamptic Brazilian women and in matched control women with an uncomplicated normal pregnancy. STUDY DESIGN: these mutations were investigated by PCR-RFLP in 83 normal pregnancies (control group) and in 30 pre-eclamptic pregnant women (severe form). RESULTS: G1691A mutation was detected neither in the control group nor in pre-eclamsia women. G20210A mutation was detected in heterozygosis in 3 (3.61%) control subjects, but not in pre-eclampsia group. C677T mutation was detected in homozygosis in 6 (7.23%) control subjects and 2 (6.67%) pre-eclamptic women and in heterozygosis in 31 (37.3%) control subjects and 12 (40%) pre-eclamptic women. Differences in the mutation frequencies detected in the two groups were not statistically significant. CONCLUSION: No correlation was observed between pre-eclampsia and presence of G1691A, G20210A and C677T mutations in Brazilian women.

Effect of oral hormone replacement therapy on plasma homocysteine levels.

BACKGROUND: Various inherited or acquired conditions can lead to mild or severe hyperhomocysteinemia, which has toxic effects on the vascular endothelium. It has been reported that hormone replacement therapy is associated with decreased homocysteine plasma levels, but this is still a controversial issue. PURPOSE: To compare homocysteine plasma levels in women before and after 3 months of oral hormone replacement therapy. METHODS: Twenty-four women were selected to take part in the study. Blood samples were collected immediately before hormone replacement therapy (cyclic association of 2 mg of estradiol valerate and 1 mg of cyproterone acetate) and three months after the beginning of hormone replacement therapy. Samples collected before hormone replacement therapy were used as controls. Plasma homocysteine levels and the presence of C677T mutation in the methylene tetrahydrofolate reductase gene were evaluated in all participants. RESULTS: The methylene tetrahydrofolate reductase gene mutation was detected in 8 women (33.3%) in heterozygosis, in 3 (12.5%) in homozygosis, and 13 women (54.2%) did not present the mutation. No significant differences were observed in homocysteine levels before and after three months of oral hormone replacement therapy, regardless of the C677T genotype. CONCLUSIONS: The results obtained indicate that homocysteine plasma levels are not affected after three months of oral hormone replacement therapy.