Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review.

Polycystic Ovary Syndrome (PCOS) is characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. This endocrinopathy is associated with many metabolic disorders such as dyslipidemia and insulin resistance, with increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular complications. Inflammation is likely to play an important role in the promoting these metabolic imbalances, while prothrombotic and pro-oxidative mechanisms further contribute to the cardiovascular risk of these patients. The etiology of PCOS is still not fully understood, but there is evidence of genetic and environmental components. This review aims to discuss some molecular pathways associated with PCOS that could contribute to the better understanding about this syndrome. Recent evidence suggests that intrauterine exposure of female mice to an excess of anti-Müllerian hormone may induce PCOS features in their post-natal life. High cytokine levels and cytokine gene polymorphisms also appear to be associated with the pathophysiology of PCOS. Furthermore, high levels of microparticles may contribute to the altered hemostasis and enhanced inflammation in PCOS. All these mechanisms may be relevant to clarify some aspects of PCOS pathogenesis and inspire new strategies to prevent the syndrome as well as treat its symptoms and mitigate the risk of long-term complications.

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome.

PURPOSE: The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. METHODS: We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers. RESULTS: Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003). CONCLUSIONS: Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.

Systemic lupus erythematosus: disease activity may influence the release of endothelial microparticles?

: To evaluate blood-borne endothelial microparticles (EMPs) in women with SLE and correlated these to disease activity as defined by the SLEDAI-2K score. The study takes cross-sectional design. A total of 90 age-matched women were recruited including: G1 (healthy volunteers, n = 30), G2 (women with SLE and low disease activity (SLEDAI-2K score ≤4; n = 30) and G3 (women with SLE and moderate/high disease activity (SLEDAI-2K score >4; n = 30). Blood was collected in 3.2% sodium citrate. Subsequently, the microparticles were purified by ultracentrifugation and labeled with anti-CD51/61 and anti-Annexin-V antibodies. Quantification and phenotyping were performed using flow cytometry. The number of EMPs was significantly higher in SLE patients compared with controls (P = 0.0178). When SLE patients were stratified according to disease activity, the number of EMPs was significantly increased in women with moderate-to-high disease activity compared with controls (P = 0.0074). We observed a correlation between the number of EMPs and age (r = -0.34; P = 0.0123) and between the number of EMPs and SLEDAI-2K score (r = 0.30; P = 0.04). Our results suggest that the SLE causes increased EMPs release, especially in patients with SLEDAI-2K score greater than 4. Although measurement of the EMPs could be useful in distinguishing patients with SLE from health controls, they have limited value in differentiating between SLE subtypes.

Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis.

The cells T CD4+ T and CD8+ can be subdivided into phenotypes naïve, T of central memory, T of effector memory and effector, according to the expression of surface molecules CD45RO and CD27. The T lymphocytes are cells of long life with capacity of rapid expansion and function, after a new antigenic exposure. In tuberculosis, it was found that specific memory T cells are present, however, gaps remain about the role of such cells in the disease immunology. In this study, the phenotypic profile was analyzed and characterized the functionality of CD4+ T lymphocytes and CD8+ T cells of memory and effector, in response to specific stimuli in vitro, in patients with active pulmonary TB, compared to individuals with latent infection with Mycobacterium tuberculosis the ones treated with pulmonary TB. It was observed that the group of patients with active pulmonary tuberculosis was the one which presented the highest proportion of cells T CD4+ of central memory IFN-É£+ e TNF-α+, suggesting that in TB, these T of central memory cells would have a profile of protective response, being an important target of study for the development of more effective vaccines; this group also developed lower proportion of CD8+ T effector lymphocytes than the others, a probable cause of specific and less effective response against the bacillus in these individuals; the ones treated for pulmonary tuberculosis were those who developed higher proportion of T CD4+ of memory central IL-17+ cells, indicating that the stimulation of long duration, with high antigenic load, followed by elimination of the pathogen, contribute to more significant generation of such cells; individuals with latent infection by M. tuberculosis and treated for pulmonary tuberculosis, showed greater response of CD8+ T effector lymphocytes IFN-É£+ than the controls, suggesting that these cells, as well as CD4+ T lymphocytes, have crucial role of protection against M. tuberculosis. These findings have contributed to a better understanding of the immunologic changes in M. tuberculosis infection and the development of new strategies for diagnosis and prevention of tuberculosis.

Creatinine and cytokines plasma levels related to HLA compatibility in kidney transplant patients / Níveis plasmáticos de creatinina e citocinas relacionados com compatibilidade HLA em pacientes transplantados renais

ABSTRACTIntroduction:The success of kidney transplantation depends on prevention of organ rejection by the recipient’s immune system, which recognizes alloantigens present in transplanted tissue. Human leukocyte antigen (HLA) typing is one of the tests used in pre-renal transplantation and represents one of the most important factors for a successful procedure.Objective:The present study evaluated creatinine and cytokines plasma levels in kidney transplant patients according to pre-transplant HLA typing.Methods:We assessed 40 renal transplanted patients selected in two transplant centers in Belo Horizonte (MG).Results:Patients were distributed into three groups according to HLA compatibility and, through statistical analysis, the group with more than three matches (H3) was found to have significantly lower post-transplant creatinine levels, compared to groups with three or fewer matches (H2 and H1, respectively). The median plasma levels of cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were evaluated according to the number of matches. Pro-inflammatory cytokines (IL-6 and TNF-α) were significantly higher in groups with lower HLA compatibility. On the other hand, the regulatory cytokine IL-10 had significantly higher plasma levels in the group with greater compatibility between donor and recipient.Conclusion:These findings allow us to infer that pre-transplant HLA typing of donors and recipients can influence post-transplant renal graft function and may contribute to the development and choice of new treatment strategies.

RESUMOIntrodução:O sucesso de um transplante renal depende da prevenção da rejeição ao órgão por parte do sistema imune do receptor ao reconhecer aloantígenos presentes no tecido transplantado. A tipagem de antígenos leucocitários humanos (HLA) é um dos testes empregados no pré-transplante renal e constitui um dos fatores mais importantes para o transplante bem-sucedido.Objetivo:O estudo em questão avaliou os níveis plasmáticos de creatinina e citocinas em pacientes transplantados renais em função da tipagem HLA realizada no período pré-transplante.Métodos:Foram avaliados 40 pacientes transplantados renais de dois centros de transplantes em Belo Horizonte (MG).Resultados:Os pacientes foram distribuídos em grupos de acordo com o número de compatibilidades HLA e constatou-se, por meio de análises estatísticas, que o grupo com mais de três compatibilidades (H3) apresentou níveis significativamente menores de creatinina pós-transplante em relação aos grupos com três ou menos compatibilidades (H2 e H1, respectivamente). As medianas dos níveis plasmáticos das citocinas interleucina 6 (IL-6), fator de necrose tumoral alfa (TNF-α) e interleucina 10 (IL-10) também foram avaliadas em função do número de compatibilidades. Observou-se que as citocinas pró-inflamatórias (IL-6 e TNF-α) estavam significativamente maiores nos grupos com menor compatibilidade HLA. Por outro lado, a citocina reguladora IL-10 apresentou níveis plasmáticos significativamente maiores no grupo com mais compatibilidades entre doador e receptor.Conclusão:Esses achados permitem inferir que a tipagem HLA de doadores e receptores pré-transplante pode influenciar na função renal do enxerto pós-transplante, bem como contribuir para o desenvolvimento e a escolha de novas estratégias de tratamento.