MAURICIO SIMOES ABRAO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina - Docente
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Macrophage Immune Memory Controls Endometriosis in Mice and Humans(2020) JELJELI, Mohamed; RICCIO, Luiza G. C.; CHOUZENOUX, Sandrine; MORESI, Fabiana; TOULLEC, Laurie; DORIDOT, Ludivine; NICCO, Carole; BOURDON, Mathilde; MARCELLIN, Louis; SANTULLI, Pietro; ABRAO, Mauricio S.; CHAPRON, Charles; BATTEUX, FredericEndometriosis is a frequent, chronic, inflammatory gynecological disease characterized by the presence of ectopic endometrial tissue causing pain and infertility. Macrophages have a central role in lesion establishment and maintenance by driving chronic inflammation and tissue remodeling. Macrophages can be reprogrammed to acquire memory-like characteristics after antigenic challenge to reinforce or inhibit a subsequent immune response, a phenomenon termed ""trained immunity.'' Here, whereas bacille Calmette-Guerin (BCG) training enhances the lesion growth in a mice model of endometriosis, tolerization with repeated low doses of lipopolysaccharide (LPSlow) or adoptive transfer of LPSlow-tolerized macrophages elicits a suppressor effect. LPSlow-tolerized human macrophages mitigate the fibro-inflammatory phenotype of endometriotic cells in an interleukin-10 (IL-10)-dependent manner. A history of severe Gram-negative infection is associated with reduced infertility duration and alleviated symptoms, in contrast to patients with Gram-positive infection history. Thus, the manipulation of innate immune memory may be effective in dampening hyper-inflammatory conditions, opening the way to promising therapeutic approaches.
- Visual Analogue Scale Cut-off Point of Seven Represents Poor Quality of Life in Patients with Endometriosis(2024) ANDRES, Marina Paula; RICCIO, Luiza Gama Coelho; ABRAO, Henrique Mendonca; MANZINI, Mariana Simionato; BRAGA, Lais; ABRAO, Mauricio SimoesEstablishing objective criteria to assess endometriosis symptoms is crucial in defining therapeutic strategies. The visual analogue scale (VAS) is the most used system to enhance the accuracy and reduce the subjectivity of pain assessment, and symptoms of endometriosis are considered severe when the VAS score is >= 7 cm. Pain symptoms can significantly impact patients' quality of life, resulting in psychological and social distress. The aim of this study is to evaluate whether a VAS cut-off point of 7 cm for each pain symptom correlates with a diminished quality of life in women with endometriosis. This retrospective study included 1129 patients who underwent surgical treatment for endometriosis. Dysmenorrhea, acyclic pelvic pain, deep dyspareunia, dyschezia, and dysuria were assessed using a 0-10 cm VAS. The Short Form-36 (SF-36) questionnaire was employed to evaluate the quality of life 6 months prior to surgery. Dysmenorrhea was the most prevalent symptom reported in 93.6% of cases, with a mean VAS of 7.6 cm. The quality of life reported was reduced in most patients, with domain scores ranging from 49.4 to 80.1. The mean SF-36 scores in all domains were significantly lower in patients with severe pain (VAS score >= 7 cm) compared to those with mild to moderate pain (VAS < 7 cm). This trend was observed across all evaluated pain symptoms. Our research demonstrates that the prevalent VAS cut-off point for establishing severe pain symptoms in endometriosis (VAS >= 7 cm) accurately represents the negative impact of the disease on women's quality of life, as assessed via the SF-36 questionnaire.
- Endometriosis and recurrent pregnancy loss: two manifestations of the same underlying dysfunction?(2023) VIDALI, Andrea; RICCIO, Luiza Gama Coelho; ABRAO, Mauricio Simoes
- B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice(2019) RICCIO, L. G. C.; JELJELI, M.; SANTULLI, P.; CHOUZENOUX, S.; DORIDOT, L.; NICCO, C.; REIS, F. M.; ABRAO, M. S.; CHAPRON, C.; BATTEUX, F.STUDY QUESTION: What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis? SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton's tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. WHAT IS KNOWN ALREADY: A polyclonal activation of B cells and the presence of anti-endometrial autoanti bodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. PARTICIPANTS/MATERIALS, SETTING, METHODS: After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinibtreated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis.
- B lymphocytes(2022) RICCIO, L. G. C.; ABRãO, M. S.Several immunological abnormalities were described in endometriosis, but their role in the pathogenesis of the disease is not completely understood. Although peritoneal immunosurveillance is mostly defective, some aspects of the immune system are upregulated, such as the widespread polyclonal activation of B lymphocytes with antibody production. Antiendometrial antibodies, IgA and IgG have been shown to be increased in endometriosis, and also anti-nuclear, antiphospholipid, and anti-DNA. It has been proposed that endometriosis may have an autoimmune etiology, as it shares common aspects with autoimmune diseases. Most drugs effective at treating endometriosis are hormonal and contraceptive, so targeting immune cells could be an alternative strategy. Btk inhibitor Ibrutinib inactivates B lymphocytes and has been recently shown to be effective in controlling disease progression in mice. Further studies should evaluate B cells subtypes and drugs that target these cells to better understand the pathogenesis and to develop new approaches to treat the disease. © 2022 Elsevier Inc. All rights reserved.
- Immunology of endometriosis(2018) RICCIO, Luiza da Gama Coelho; SANTULLI, Pietro; MARCELLIN, Louis; ABRAO, Mauricio Simoes; BATTEUX, Frederic; CHAPRON, CharlesThe pathophysiology of endometriosis is not completely under stood, but an aberrant immune response in the peritoneal environment seems to be crucial for the proliferation of ectopic endometrial cells as those cells escape apoptosis and peritoneal cavity immunosurveillance. The growth of endometrial implants leads to the recruitment of a large number and diversity of immune cells and intense inflammation with increased pro inflammatory cytokines, growth factors, and angiogenesis. There is substantial evidence of aberrant function of almost all types of immune cells in women with endometriosis: decreased T cell reactivity and NK cytotoxicity, polyclonal activation of B cells and increased antibody production, increased number and activation of peritoneal macrophages, and changes in inflammatory mediators. New clinical treatments for endometriosis are an urgent need, especially nonhormonal drugs. The study of immunology may clarify its role in the pathogenesis of endometriosis and contribute to the development of new therapeutic strategies.
- p The role of dendritic cells in endometriosis: A systematic review(2022) LAGINHA, Paulo Arantes; ARCOVERDE, Fernanda Vieira Lins; RICCIO, Luiza Gama Coelho; ANDRES, Marina Paula; ABRAO, Mauricio SimoesEndometriosis (EDT), a common estrogen-dependent inflammatory disorder, is characterized by endometrial-like tissue outside the uterus. While its pathogenesis is poorly understood, it is supposed that the immune system plays a role in its pathophysiology, and increased number of immune cells and changes in both cell-mediated and humoral immunity have been described. Dendritic cells (DCs) are antigen-presenting cells (APC) of the immune system that recognize, capture, and process complex antigens and present them to T cells, conferring them a unique ability as mediators between the innate and adaptive immune systems. This systematic review aims to enlighten possible disturbances (systemically and locally) of DCs in the development and progression of endometriosis. A search using the strategy: (""dendritic cells"" AND ""immunology"" AND ""endometriosis"") in databases resulted in 490 citations; after applying inclusion and exclusion criteria, a total of 13 studies were assessed. The evaluated studies demonstrated that DCs are susceptible to pro-endometriotic changes which could inhibit immature DCs (imDCs) from their maturation and induce imDCs into a macrophage phenotype. In addition, the growth and vascularization of endometriosis requires the presence of endogenous DC, which infiltrate endometriotic lesions and enhance endothelial cell migration by secreting proangiogenic factors. Whereas DC maturation suppresses this response, imDC actively promote angiogenesis and growth, leading to a switch in their immunologic role from presenting antigens to support angiogenesis and EDT progression.
- The role of the B lymphocytes in endometriosis: A systematic review(2017) RICCIO, L. G. C.; BARACAT, E. C.; CHAPRON, C.; BATTEUX, F.; ABRAO, M. S.The physiopathology of endometriosis is not completely understood and its progression is associated with a local and systemic inflammatory reaction. It is important to clarify the potential role of the immune system to better understand its implication in the pathogenesis of endometriosis, which includes the study of the role of B cells and antibodies. The aim of this study was to review the literature about the role of B lymphocytes in endometriosis. A search for ""endometriosis"", ""B cells"" and ""B lymphocytes"" in databases resulted in 140 citations; after applying inclusion and exclusion criteria, a total of 22 studies were assessed. The analyzed samples in the studies varied and different markers and techniques were used by the authors to evaluate the direct or indirect role of B lymphocytes in endometriosis. Most studies demonstrated increased number and/or activation of B cells while seven studies found no difference and two studies showed decreased number of B cells. Increased B lymphocytes and excessive production of autoantibodies in endometriosis have been described in the literature, but their role in the development of the disease is not well understood. Moreover, the association of these factors with clinical symptoms, location and severity of the disease has not been investigated. Further studies are necessary to clarify the role of B cells in the development of endometriosis and propose new therapeutic strategies such as the use of drugs that target these cells.