Ronei Luciano Mamoni - Academia.edu (original) (raw)
Papers by Ronei Luciano Mamoni
Diversos estudos demonstram que a resposta inflamatoria e de extrema importância para o controle ... more Diversos estudos demonstram que a resposta inflamatoria e de extrema importância para o controle da Paracoccidioidomicose (PCM). Essa resposta inflamatoria e iniciada pelo reconhecimento das celulas fungicas por receptores expressos por celulas do sistema imunologico inato. Dentre esses receptores, o NLRP3 foi associado com o reconhecimento de fungos patogenicos em modelos experimentais, atuando em conjunto com o TLR2 e a dectina-1. O NLRP3 atua na formacao de um complexo multiproteico denominado inflamassoma, o qual ativa a caspase-1, que e responsavel pela producao das formas ativas de duas importantes citocinas inflamatorias: a IL-1? e a IL-18. Esse estudo teve por objetivo investigar o envolvimento do NLRP3 na ativacao da resposta inflamatoria de macrofagos e celulas dendriticas humanas (DCs) derivadas de monocitos em resposta ao Paracoccidioides brasiliensis (Pb), alem de avaliar a participacao do NLRP3 na inducao da resposta imunologica adaptativa. Nossos resultados demonstrar...
BMC Geriatrics
Background To investigate whether an exercise intervention using the VIVIFRAIL© protocol has bene... more Background To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status. Methods/design This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change...
BMC Psychiatry
Background To explore the mutual relationship between multimorbidity, mental illness and frailty,... more Background To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression an...
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
The Brazilian Journal of Infectious Diseases
The Journal of infection, Jan 7, 2018
To investigate the involvement of NLRP3 in the effector functions of human dendritic cells (DCs) ... more To investigate the involvement of NLRP3 in the effector functions of human dendritic cells (DCs) in response to Paracoccidioides brasiliensis yeast cells (Pb) and to evaluate its role in the modulation of the adaptive immune response. DCs were differentiated from purified peripheral blood monocytes and analyzed in relation to the participation of TLR-2, dectin-1, and Syk in Pb recognition, as well as, the indirect mechanisms (Reactive Oxygen Species production, endosome acidification, or K efflux) involved in NLRP3 inflammasome activation after the stimulus with Pb. Additionally, we analyzed the role of NLRP3 in the activation of T cells. Our results demonstrated that the NLRP3 inflammasome activation and cytokines production by DCs are dependent on ROS generation, endosome acidification, and K efflux and involve the Pb recognition by dectin-1 and Syk phosphorylation. Our data also demonstrate that the NLRP3 inflammasome is essential for the activation/expansion of Th1/Th17 cells an...
Clinics (Sao Paulo, Brazil), 2018
Articular cartilage is vulnerable to injuries and undergoes an irreversible degenerative process.... more Articular cartilage is vulnerable to injuries and undergoes an irreversible degenerative process. The use of amniotic fluid mesenchymal stromal stem cells for the reconstruction of articular cartilage is a promising therapeutic alternative. The aim of this study was to investigate the chondrogenic potential of amniotic fluid mesenchymal stromal stem cells from human amniotic fluid from second trimester pregnant women in a micromass system (high-density cell culture) with TGF-β3 for 21 days. Micromass was performed using amniotic fluid mesenchymal stromal stem cells previously cultured in a monolayer. Chondrocytes from adult human normal cartilage were used as controls. After 21 days, chondrogenic potential was determined by measuring the expression of genes, such as SOX-9, type II collagen and aggrecan, in newly differentiated cells by real-time PCR (qRT-PCR). The production of type II collagen protein was observed by western blotting. Immunohistochemistry analysis was also performe...
Pigment cell & melanoma research, Mar 1, 2017
This study aimed to evaluate whether PD1.1 (c.-606G>A), PD1 (c.627+252C>T), PD1.5 (c.804C&g... more This study aimed to evaluate whether PD1.1 (c.-606G>A), PD1 (c.627+252C>T), PD1.5 (c.804C>T) and PD1.9 (c.644C>T) single nucleotide polymorphisms of PDCD1 gene influence the risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Individuals with phototype I or II and PD1 CC genotype were under 5.89-fold increased risk of developing CM. PD1.5 TT genotype increased PDCD1 expression (2.49 vs. 1.28 arbitrary units, P= 0.03) and PD1.5 CT or TT genotype and allele T increased PD1 expression in TCD4(+) lymphocytes (16.6 vs. 12.5%, P= 0.01; 17.0 vs. 13.1%, P= 0.006). At 60 months of follow-up, short recurrence-free survival was seen in patients with PD1.1 AA genotype (33.3 vs. 71.8%, P= 0.03). Patients with PD1.1 AA and PD1.5 CC genotype had 4.21 and 2.62 more chances of presenting relapse and evolving death by disease in Cox analyses, respectively. Our data provides preliminary evidence that abnormalities in regulation of T-lymphocyte alter CM risk, clinical...
Medical Mycology
Besides interleukin (IL)-1β and IL-18, the newly described cytokines of IL-1 family IL-33 and IL-... more Besides interleukin (IL)-1β and IL-18, the newly described cytokines of IL-1 family IL-33 and IL-37 can contribute to the differentiation and maintenance of different population of T cells. IL-33 acts as an allarmin and promotes a predominant Th2 inflammatory response, whereas IL-37 plays an important role as an antagonist of inflammation. In paracoccidioidomycosis (PCM), caused by the dimorphic fungi Paracoccidioides brasiliensis and P. lutzii, it has been shown that the acquired immune responses are associated with the diverse clinical manifestations. The severe and disseminated forms (acute form [AF] and multifocal chronic form [CF-MF]) are characterized by high Th2 cytokines and antibody production, impaired cellular immune response, and eosinophilia. In contrast, in the localized form (unifocal chronic form [CF-UF]), the cellular immune response is preserved, with high production of Th1 and Th17 cytokines, and low antibody titers. This study aimed to quantify interleukin-1 family cytokines (IL-1β, IL-18, IL-37, IL-33, and the soluble IL-33 receptor sST2) in sera of patients presenting different clinical forms of PCM before, during, and after antifungal treatment, as well as to analyze the expression of these cytokines in lesions of PCM patients. We found that AF patients presented high serum levels of IL-1β, IL-18, IL-33, sST2, and IL-37, and that these cytokines are strongly expressed 332
PLoS neglected tropical diseases, 2017
Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a s... more Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower populatio...
Journal of Reproductive Immunology, Jun 1, 2004
Cytokines seem to play a critical role in the pathogenesis of unexplained recurrent pregnancy los... more Cytokines seem to play a critical role in the pathogenesis of unexplained recurrent pregnancy loss (RPL). Th1 cytokines have been shown to exert deleterious effects on pregnancy, inhibiting foetal growth and development. On the other hand, Th2 cytokines have been associated with successful pregnancy. The purpose of this study was to evaluate cytokine production in women with RPL. The studied group comprised 29 women with RPL, with at least three consecutive spontaneous abortions. The control group included 27 women with a history of successful pregnancies and no miscarriage. We determined IL-6 and TNF-alpha production in peripheral blood cultured with LPS, as well as IFN-gamma and TGF-beta induced by PHA stimulation. Cytokines were measured by enzyme-linked immunoabsorbant assay (ELISA) using commercial kits (RD, Amersham-Pharmacia). Mann-Whitney test was applied to compare differences between groups. The level of significance was defined at P < 0.05. We observed significantly higher levels of IFN-gamma (355.8 pg/ml versus 98.0 pg/ml; P = 0.01) and a trend toward increased TNF-alpha production (2410.2 pg/ml versus1980.2 pg/ml; P = 0.07) in RPL women as compared to controls. In relation to IL-6 and TGF-beta, no significant difference was detected between RPL and control groups. In agreement with experimental observations, our data support the hypothesis of Th1 cytokine involvement in the pathogenesis of RPL.
Cytokine, 2005
The human infection with Paracoccidioides brasiliensis may result in three major outcomes: the pa... more The human infection with Paracoccidioides brasiliensis may result in three major outcomes: the paracoccidioidomycosis-infection (PI), the adult form (AF) and the juvenile form (JF) of the disease. The aim of this study was to compare the immunological response among these groups. The gene expression of multiple cytokines, including IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha and TGF-beta1, and chemokines, CXCL8, CXCL9 and CXCL10 was evaluated by RT-PCR in peripheral blood mononuclear cells unstimulated or following phytohemagglutinin stimulation for 3, 6, 12, 24 and 48 h. PI individuals expressed earlier and higher levels of mRNA of IFN-gamma, TNF-alpha, CXCL9 and CXCL10 when compared to JF patients. In relation to AF patients, the PI group presented similar levels of CXCL10 and IFN-gamma and higher levels of CXCL9. On the other hand, mRNA expression of Th2 cytokines (IL-4, IL-10, IL-5 and TGF-beta1) was higher and earlier in JF and AF groups, when compared to PI individuals. At some time intervals it was possible to differentiate JF from AF, mainly in relation to IL-4 and TGF-beta1 mRNA, expressed in higher levels in the JF patients. The distinct patterns of cytokines and chemokines expression support their important role in determining the different outcomes observed in this disease.
Microbes and Infection, Feb 28, 2002
Cellular immune response to Paracoccidiodes brasiliensis antigens (PbAg) was evaluated in patient... more Cellular immune response to Paracoccidiodes brasiliensis antigens (PbAg) was evaluated in patients with the juvenile (JF) and adult (AF) forms of paracoccidioidomycosis as well as in a group of infected individuals living in the endemic area but without any clinical manifestation of the disease. The immune profile of this group of paracoccidioidomycosis-infected individuals was characterized by: 1) a positive skin test to P. brasiliensis antigen; 2) absence of specific antibodies; 3) a vigorous lymphoproliferative response to PbAg; and 4) a typical Th1 pattern of cytokines, with production of IFN-gamma and basal levels of IL-4, IL-5 and IL-10. At the opposite end of the spectrum were the JF patients whose proliferative response to PbAg was significantly impaired and whose cytokine pattern was characteristically Th2, i.e. lower IFN-gamma secretion and significantly higher levels of IL-4, IL-5 and IL-10. These profiles are compatible with forms of higher and lower resistance, respectively. Intermediate immune responses were observed in AF patients, whose specific lymphoproliferative response was lower than in the paracoccidioidomycosis-infected group but higher than in the JF patients. The secretion of IFN-gamma and IL-10 did not differ from the JF group, although IL-4 and IL-5 levels were significantly lower. Since AF patients are able to control fungal dissemination for decades, they can be considered more resistant than JF patients, who manifest the disease soon after infection.
Circulation, Oct 31, 2006
The American journal of tropical medicine and hygiene, 1999
This paper describes the clinical-seroepidemiologic characteristics of patients with paracoccidio... more This paper describes the clinical-seroepidemiologic characteristics of patients with paracoccidioidomycosis (PCM) who visited the University Hospital at the State University of Campinas (Campinas, Sao Paulo, Brazil). The study group consisted of 584 individuals (492 males and 92 females) with ages ranging from 5 to 87 years. The highest incidence of the disease occurred between the ages of 41 and 50 years for men and between 11 and 40 years for women. Rural activities were the principal occupation of 46% of the patients. The diagnosis was confirmed by histopathologic examination and demonstration of fungus in scrapings, secretions, or in the sputum. Serologic test results for PCM were positive in 80% of the 584 patients studied. The significant number of patients, including 33 children less than 14 years old, indicates the presence of the fungus in the area and that this region is an important endemic area for PCM.
The American journal of tropical medicine and hygiene, 2001
Paracoccidioidomycosis (PCM) is the most frequent systemic mycosis in South America. The disease ... more Paracoccidioidomycosis (PCM) is the most frequent systemic mycosis in South America. The disease is characterized by a polyclonal activation of B cells, resulting in hyperimmunoglobulinemia. The production of immunoglobulin (Ig) E in deep mycosis has been related to the severity of the disease. However, the detection of specific IgE in sera of patients is difficult because of the competition with the IgG. We compared a capture and an indirect enzyme-linked immunosorbent assay (ELISA) technique to detect Paracoccidioides brasiliensis IgE. We found that the capture ELISA presented higher performance and lower background values than the indirect assay, resulting in a significant quantitative discrimination between sera from patients with the 2 major clinical forms of PCM. Patients with the juvenile form presented significantly higher levels of P. brasiliensis IgE, as compared with patients with the adult form. The capture ELISA was used in the follow-up of patients receiving treatment,...
Diversos estudos demonstram que a resposta inflamatoria e de extrema importância para o controle ... more Diversos estudos demonstram que a resposta inflamatoria e de extrema importância para o controle da Paracoccidioidomicose (PCM). Essa resposta inflamatoria e iniciada pelo reconhecimento das celulas fungicas por receptores expressos por celulas do sistema imunologico inato. Dentre esses receptores, o NLRP3 foi associado com o reconhecimento de fungos patogenicos em modelos experimentais, atuando em conjunto com o TLR2 e a dectina-1. O NLRP3 atua na formacao de um complexo multiproteico denominado inflamassoma, o qual ativa a caspase-1, que e responsavel pela producao das formas ativas de duas importantes citocinas inflamatorias: a IL-1? e a IL-18. Esse estudo teve por objetivo investigar o envolvimento do NLRP3 na ativacao da resposta inflamatoria de macrofagos e celulas dendriticas humanas (DCs) derivadas de monocitos em resposta ao Paracoccidioides brasiliensis (Pb), alem de avaliar a participacao do NLRP3 na inducao da resposta imunologica adaptativa. Nossos resultados demonstrar...
BMC Geriatrics
Background To investigate whether an exercise intervention using the VIVIFRAIL© protocol has bene... more Background To investigate whether an exercise intervention using the VIVIFRAIL© protocol has benefits for inflammatory and functional parameters in different frailty status. Methods/design This is a randomized clinical trial in an outpatient geriatrics clinic including older adults ≥60 years. For each frailty state (frail, pre-frail and robust), forty-four volunteers will be randomly allocated to the control group (n = 22) and the intervention group (n = 22) for 12 weeks. In the control group, participants will have meetings of health education while those in the intervention group will be part of a multicomponent exercise program (VIVIFRAIL©) performed five times a week (two times supervised and 3 times of home-based exercises). The primary outcome is a change in the inflammatory profile (a reduction in inflammatory interleukins [IL-6, TNF- α, IL1beta, IL-17, IL-22, CXCL-8, and IL-27] or an increase in anti-inflammatory mediators [IL-10, IL1RA, IL-4]). Secondary outcomes are change...
BMC Psychiatry
Background To explore the mutual relationship between multimorbidity, mental illness and frailty,... more Background To explore the mutual relationship between multimorbidity, mental illness and frailty, we have set-up the Multimorbidity and Mental health Cohort Study in FRAILty and Aging (MiMiCS-FRAIL) cohort. At the population level, multimorbidity, frailty and late-life depression are associated with similar adverse outcomes (i.e. falls, disability, hospitalization, death), share the same risk factors, and partly overlap in their clinical presentation. Moreover, these three variables may share a common underlying pathophysiological mechanism like immune-metabolic dysregulation. The overall objectives of MiMiCS-FRAIL are 1) to explore (determinants of) the cross-sectional and longitudinal relationship between multimorbidity, depression, and frailty among non-demented geriatric outpatients; 2) to evaluate molecular levels of senoinflammation as a broad pathophysiological process underlying these conditions; and 3) to examine adverse outcomes of multimorbidity, frailty and depression an...
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
Anais do XVI Fórum de Iniciação Científica PIBIC-FMJ-CNPq
The Brazilian Journal of Infectious Diseases
The Journal of infection, Jan 7, 2018
To investigate the involvement of NLRP3 in the effector functions of human dendritic cells (DCs) ... more To investigate the involvement of NLRP3 in the effector functions of human dendritic cells (DCs) in response to Paracoccidioides brasiliensis yeast cells (Pb) and to evaluate its role in the modulation of the adaptive immune response. DCs were differentiated from purified peripheral blood monocytes and analyzed in relation to the participation of TLR-2, dectin-1, and Syk in Pb recognition, as well as, the indirect mechanisms (Reactive Oxygen Species production, endosome acidification, or K efflux) involved in NLRP3 inflammasome activation after the stimulus with Pb. Additionally, we analyzed the role of NLRP3 in the activation of T cells. Our results demonstrated that the NLRP3 inflammasome activation and cytokines production by DCs are dependent on ROS generation, endosome acidification, and K efflux and involve the Pb recognition by dectin-1 and Syk phosphorylation. Our data also demonstrate that the NLRP3 inflammasome is essential for the activation/expansion of Th1/Th17 cells an...
Clinics (Sao Paulo, Brazil), 2018
Articular cartilage is vulnerable to injuries and undergoes an irreversible degenerative process.... more Articular cartilage is vulnerable to injuries and undergoes an irreversible degenerative process. The use of amniotic fluid mesenchymal stromal stem cells for the reconstruction of articular cartilage is a promising therapeutic alternative. The aim of this study was to investigate the chondrogenic potential of amniotic fluid mesenchymal stromal stem cells from human amniotic fluid from second trimester pregnant women in a micromass system (high-density cell culture) with TGF-β3 for 21 days. Micromass was performed using amniotic fluid mesenchymal stromal stem cells previously cultured in a monolayer. Chondrocytes from adult human normal cartilage were used as controls. After 21 days, chondrogenic potential was determined by measuring the expression of genes, such as SOX-9, type II collagen and aggrecan, in newly differentiated cells by real-time PCR (qRT-PCR). The production of type II collagen protein was observed by western blotting. Immunohistochemistry analysis was also performe...
Pigment cell & melanoma research, Mar 1, 2017
This study aimed to evaluate whether PD1.1 (c.-606G>A), PD1 (c.627+252C>T), PD1.5 (c.804C&g... more This study aimed to evaluate whether PD1.1 (c.-606G>A), PD1 (c.627+252C>T), PD1.5 (c.804C>T) and PD1.9 (c.644C>T) single nucleotide polymorphisms of PDCD1 gene influence the risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Individuals with phototype I or II and PD1 CC genotype were under 5.89-fold increased risk of developing CM. PD1.5 TT genotype increased PDCD1 expression (2.49 vs. 1.28 arbitrary units, P= 0.03) and PD1.5 CT or TT genotype and allele T increased PD1 expression in TCD4(+) lymphocytes (16.6 vs. 12.5%, P= 0.01; 17.0 vs. 13.1%, P= 0.006). At 60 months of follow-up, short recurrence-free survival was seen in patients with PD1.1 AA genotype (33.3 vs. 71.8%, P= 0.03). Patients with PD1.1 AA and PD1.5 CC genotype had 4.21 and 2.62 more chances of presenting relapse and evolving death by disease in Cox analyses, respectively. Our data provides preliminary evidence that abnormalities in regulation of T-lymphocyte alter CM risk, clinical...
Medical Mycology
Besides interleukin (IL)-1β and IL-18, the newly described cytokines of IL-1 family IL-33 and IL-... more Besides interleukin (IL)-1β and IL-18, the newly described cytokines of IL-1 family IL-33 and IL-37 can contribute to the differentiation and maintenance of different population of T cells. IL-33 acts as an allarmin and promotes a predominant Th2 inflammatory response, whereas IL-37 plays an important role as an antagonist of inflammation. In paracoccidioidomycosis (PCM), caused by the dimorphic fungi Paracoccidioides brasiliensis and P. lutzii, it has been shown that the acquired immune responses are associated with the diverse clinical manifestations. The severe and disseminated forms (acute form [AF] and multifocal chronic form [CF-MF]) are characterized by high Th2 cytokines and antibody production, impaired cellular immune response, and eosinophilia. In contrast, in the localized form (unifocal chronic form [CF-UF]), the cellular immune response is preserved, with high production of Th1 and Th17 cytokines, and low antibody titers. This study aimed to quantify interleukin-1 family cytokines (IL-1β, IL-18, IL-37, IL-33, and the soluble IL-33 receptor sST2) in sera of patients presenting different clinical forms of PCM before, during, and after antifungal treatment, as well as to analyze the expression of these cytokines in lesions of PCM patients. We found that AF patients presented high serum levels of IL-1β, IL-18, IL-33, sST2, and IL-37, and that these cytokines are strongly expressed 332
PLoS neglected tropical diseases, 2017
Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a s... more Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower populatio...
Journal of Reproductive Immunology, Jun 1, 2004
Cytokines seem to play a critical role in the pathogenesis of unexplained recurrent pregnancy los... more Cytokines seem to play a critical role in the pathogenesis of unexplained recurrent pregnancy loss (RPL). Th1 cytokines have been shown to exert deleterious effects on pregnancy, inhibiting foetal growth and development. On the other hand, Th2 cytokines have been associated with successful pregnancy. The purpose of this study was to evaluate cytokine production in women with RPL. The studied group comprised 29 women with RPL, with at least three consecutive spontaneous abortions. The control group included 27 women with a history of successful pregnancies and no miscarriage. We determined IL-6 and TNF-alpha production in peripheral blood cultured with LPS, as well as IFN-gamma and TGF-beta induced by PHA stimulation. Cytokines were measured by enzyme-linked immunoabsorbant assay (ELISA) using commercial kits (RD, Amersham-Pharmacia). Mann-Whitney test was applied to compare differences between groups. The level of significance was defined at P < 0.05. We observed significantly higher levels of IFN-gamma (355.8 pg/ml versus 98.0 pg/ml; P = 0.01) and a trend toward increased TNF-alpha production (2410.2 pg/ml versus1980.2 pg/ml; P = 0.07) in RPL women as compared to controls. In relation to IL-6 and TGF-beta, no significant difference was detected between RPL and control groups. In agreement with experimental observations, our data support the hypothesis of Th1 cytokine involvement in the pathogenesis of RPL.
Cytokine, 2005
The human infection with Paracoccidioides brasiliensis may result in three major outcomes: the pa... more The human infection with Paracoccidioides brasiliensis may result in three major outcomes: the paracoccidioidomycosis-infection (PI), the adult form (AF) and the juvenile form (JF) of the disease. The aim of this study was to compare the immunological response among these groups. The gene expression of multiple cytokines, including IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha and TGF-beta1, and chemokines, CXCL8, CXCL9 and CXCL10 was evaluated by RT-PCR in peripheral blood mononuclear cells unstimulated or following phytohemagglutinin stimulation for 3, 6, 12, 24 and 48 h. PI individuals expressed earlier and higher levels of mRNA of IFN-gamma, TNF-alpha, CXCL9 and CXCL10 when compared to JF patients. In relation to AF patients, the PI group presented similar levels of CXCL10 and IFN-gamma and higher levels of CXCL9. On the other hand, mRNA expression of Th2 cytokines (IL-4, IL-10, IL-5 and TGF-beta1) was higher and earlier in JF and AF groups, when compared to PI individuals. At some time intervals it was possible to differentiate JF from AF, mainly in relation to IL-4 and TGF-beta1 mRNA, expressed in higher levels in the JF patients. The distinct patterns of cytokines and chemokines expression support their important role in determining the different outcomes observed in this disease.
Microbes and Infection, Feb 28, 2002
Cellular immune response to Paracoccidiodes brasiliensis antigens (PbAg) was evaluated in patient... more Cellular immune response to Paracoccidiodes brasiliensis antigens (PbAg) was evaluated in patients with the juvenile (JF) and adult (AF) forms of paracoccidioidomycosis as well as in a group of infected individuals living in the endemic area but without any clinical manifestation of the disease. The immune profile of this group of paracoccidioidomycosis-infected individuals was characterized by: 1) a positive skin test to P. brasiliensis antigen; 2) absence of specific antibodies; 3) a vigorous lymphoproliferative response to PbAg; and 4) a typical Th1 pattern of cytokines, with production of IFN-gamma and basal levels of IL-4, IL-5 and IL-10. At the opposite end of the spectrum were the JF patients whose proliferative response to PbAg was significantly impaired and whose cytokine pattern was characteristically Th2, i.e. lower IFN-gamma secretion and significantly higher levels of IL-4, IL-5 and IL-10. These profiles are compatible with forms of higher and lower resistance, respectively. Intermediate immune responses were observed in AF patients, whose specific lymphoproliferative response was lower than in the paracoccidioidomycosis-infected group but higher than in the JF patients. The secretion of IFN-gamma and IL-10 did not differ from the JF group, although IL-4 and IL-5 levels were significantly lower. Since AF patients are able to control fungal dissemination for decades, they can be considered more resistant than JF patients, who manifest the disease soon after infection.
Circulation, Oct 31, 2006
The American journal of tropical medicine and hygiene, 1999
This paper describes the clinical-seroepidemiologic characteristics of patients with paracoccidio... more This paper describes the clinical-seroepidemiologic characteristics of patients with paracoccidioidomycosis (PCM) who visited the University Hospital at the State University of Campinas (Campinas, Sao Paulo, Brazil). The study group consisted of 584 individuals (492 males and 92 females) with ages ranging from 5 to 87 years. The highest incidence of the disease occurred between the ages of 41 and 50 years for men and between 11 and 40 years for women. Rural activities were the principal occupation of 46% of the patients. The diagnosis was confirmed by histopathologic examination and demonstration of fungus in scrapings, secretions, or in the sputum. Serologic test results for PCM were positive in 80% of the 584 patients studied. The significant number of patients, including 33 children less than 14 years old, indicates the presence of the fungus in the area and that this region is an important endemic area for PCM.
The American journal of tropical medicine and hygiene, 2001
Paracoccidioidomycosis (PCM) is the most frequent systemic mycosis in South America. The disease ... more Paracoccidioidomycosis (PCM) is the most frequent systemic mycosis in South America. The disease is characterized by a polyclonal activation of B cells, resulting in hyperimmunoglobulinemia. The production of immunoglobulin (Ig) E in deep mycosis has been related to the severity of the disease. However, the detection of specific IgE in sera of patients is difficult because of the competition with the IgG. We compared a capture and an indirect enzyme-linked immunosorbent assay (ELISA) technique to detect Paracoccidioides brasiliensis IgE. We found that the capture ELISA presented higher performance and lower background values than the indirect assay, resulting in a significant quantitative discrimination between sera from patients with the 2 major clinical forms of PCM. Patients with the juvenile form presented significantly higher levels of P. brasiliensis IgE, as compared with patients with the adult form. The capture ELISA was used in the follow-up of patients receiving treatment,...