RESUMO
Background: Intra-amniotic umbilical vein varices are characterized by a focal dilatation of the extra abdominal umbilical vein. Case report: We report a full-term baby female with extra-abdominal umbilical vein varices misdiagnosed clinically as an omphalocele. The umbilical vein was ligated and excised near the level of the liver. The infant died one day after surgery due to extrinsic compression of the renal pedicle by a massive thrombus, resulting in severe renal failure and life-threatening hyperkalemia despite intensive resuscitation. Conclusion: Large intra-amniotic umbilical vein varices can be clinically misdiagnosed as an omphalocele. Their resection near the level of the fascia, as with normal umbilical veins, could be a better management with a better prognosis.
Assuntos
Hérnia Umbilical , Varizes , Gravidez , Humanos , Feminino , Veias Umbilicais , Hérnia Umbilical/diagnóstico , Ultrassonografia Pré-Natal , Varizes/diagnóstico , Erros de DiagnósticoRESUMO
The aromatic hydrocarbons receptor (AhR) is a ligand-dependent transcription factor that plays a role in mediating toxicity to xenobiotics. Its key role in immune regulation has been recently demonstrated. Recent data pointed to the efficacy of ITE (2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester), a nontoxic ligand of AhR, in experimental models of inflammatory diseases. Such effect was mainly through the expansion of regulatory T cells (Tregs). Similarly, TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a toxic ligand of AhR, has been shown to exert comparable effects on Tregs in mice. Herein, we showed that ITE has no effects on natural Tregs. However, it supports the de novo generation of Tregs in humans while promoting their suppressive functions. Our data bring new elements supporting the use of ITE in human therapy of inflammatory diseases.
Assuntos
Receptores de Hidrocarboneto Arílico/metabolismo , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Adulto , Humanos , Indóis/farmacologia , Ligantes , Linfócitos T Reguladores/efeitos dos fármacos , Tiazóis/farmacologiaAssuntos
Alopecia em Áreas/genética , Fatores de Transcrição Forkhead/genética , RNA Mensageiro/metabolismo , Transcrição Gênica , Adolescente , Adulto , Alopecia em Áreas/imunologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Pele/metabolismo , Linfócitos T Reguladores , Adulto JovemRESUMO
We report a case of giant cardiac tumor diagnosed at fetal life and thought to be a fibroma. Six months later, a marked regression of the tumor size was observed. Diagnosis of rhabdomyoma was retrospectively made. Tuberous sclerosis was then suspected and MRI showed many signs of consistent diagnosis.
Assuntos
Fibroma/diagnóstico , Neoplasias Cardíacas/diagnóstico , Rabdomioma/diagnóstico , Adulto , Ecocardiografia , Feminino , Fibroma/diagnóstico por imagem , Idade Gestacional , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Regressão Neoplásica Espontânea , Gravidez , Rabdomioma/diagnóstico por imagem , Esclerose Tuberosa/diagnóstico , Ultrassonografia Pré-NatalRESUMO
OBJECTIVES: Regulatory T cells (Tregs) are instrumental for tolerance to self-antigens and dietary proteins. We have previously shown that interleukin (IL)-15, a cytokine overexpressed in the intestine of patients with celiac disease (CD), does not impair the generation of functional Tregs but renders human T cells resistant to Treg suppression. Treg numbers and responses of intestinal and peripheral T lymphocytes to suppression by Tregs were therefore compared in CD patients and controls. METHODS: Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) were isolated from duodenal biopsy specimens of CD patients and controls. Concomitantly, CD4+CD25+ T lymphocytes (Tregs) were purified from blood. Responses of IELs and of LPLs, and peripheral lymphocytes (PBLs) to suppression by Tregs were tested by analyzing anti-CD3-induced proliferation and interferon (IFN)-γ production in the presence or absence of peripheral Tregs. Lamina propria and peripheral CD4+CD25+FOXP3+ T cells were assessed by flow cytometry. RESULTS: Although percentages of CD4+CD25+FOXP3+ LPLs were significantly increased in patients with active CD, proliferation and IFN-γ production of intestinal T lymphocytes were significantly less inhibited by autologous or heterologous Tregs in CD patients than in controls (P < 0.01). In all tested CD patients, IEL were unable to respond to Tregs. Resistance of LPLs and PBLs to Treg suppression was observed in patients with villous atrophy who had significantly enhanced serum levels of IL-15 compared with patients without villous atrophy and controls. CONCLUSIONS: Our results indicate that effector T lymphocytes from active CD become resistant to suppression by Tregs. This resistance might cause loss of tolerance to gluten, but also to self-antigens.
Assuntos
Doença Celíaca/imunologia , Interleucina-15/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Autoimunidade , Biópsia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Estudos de Casos e Controles , Doença Celíaca/metabolismo , Duodeno/citologia , Duodeno/metabolismo , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Tolerância Imunológica , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-15/metabolismo , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não Paramétricas , Linfócitos T Reguladores/metabolismoRESUMO
BACKGROUND: The saliva of sand flies strongly enhances the infectivity of Leishmania in mice. Additionally, pre-exposure to saliva can protect mice from disease progression probably through the induction of a cellular immune response. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the cellular immune response against the saliva of Phlebotomus papatasi in humans and defined the phenotypic characteristics and cytokine production pattern of specific lymphocytes by flow cytometry. Additionally, proliferation and IFN-γ production of activated cells were analysed in magnetically separated CD4+ and CD8+ T cells. A proliferative response of peripheral blood mononuclear cells against the saliva of Phlebotomus papatasi was demonstrated in nearly 30% of naturally exposed individuals. Salivary extracts did not induce any secretion of IFN-γ but triggered the production of IL-10 primarily by CD8+ lymphocytes. In magnetically separated lymphocytes, the saliva induced the proliferation of both CD4+ and CD8+ T cells which was further enhanced after IL-10 blockage. Interestingly, when activated CD4+ lymphocytes were separated from CD8+ cells, they produced high amounts of IFN-γ. CONCLUSION: Herein, we demonstrated that the overall effect of Phlebotomus papatasi saliva was dominated by the activation of IL-10-producing CD8+ cells suggesting a possible detrimental effect of pre-exposure to saliva on human leishmaniasis outcome. However, the activation of Th1 lymphocytes by the saliva provides the rationale to better define the nature of the salivary antigens that could be used for vaccine development.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interleucina-10/metabolismo , Phlebotomus/imunologia , Células Th1/imunologia , Adolescente , Adulto , Idoso , Animais , Proliferação de Células , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Saliva/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto JovemRESUMO
BACKGROUND: The mechanisms underlying the loss of self-tolerance in systemic lupus erythematosus (SLE) are incompletely deciphered. TGF-ß plays a key role in self-tolerance demonstrated by the onset of a fatal autoimmune syndrome associated with lupus autoantibodies in mice lacking a functional TGF-ß receptor. The present work aims to define whether resistance to TGF-ß might contribute to the pathogenesis of SLE. METHODS: Twenty-two patients with active SLE, 16 with other connective tissue diseases, and 10 healthy controls were prospectively included in this study. The effects of exogenous TGF-ß1 on IL-2-dependent T-cell proliferation, IFN-γ secretion, and target gene transcription were analyzed on peripheral blood mononuclear cells. RESULTS: Our results showed that 75% of patients with SLE or other connective tissue diseases were totally or partially resistant to the effects of TGF-ß1. The responses to the anti-proliferative and transcriptional effects of TGF-ß were, however, discordant in a high proportion of our patients. Hence, we distinguish three distinct profiles of resistance to TGF-ß1 and suggest that patients may exhibit different defects affecting distinct points of TGF-ß1 signaling pathways. CONCLUSION: Our data demonstrate the presence of an impaired response of peripheral cells to TGF-ß1 in patients with active SLE that may participate to the pathogenesis of the disease. Further studies will be necessary to delineate the mechanisms underlying the lymphocyte resistance to TGF-ß1 in SLE.
Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Linfócitos T/imunologia , Fator de Crescimento Transformador beta/farmacologia , Adolescente , Adulto , Proliferação de Células , Feminino , Humanos , Tolerância Imunológica , Interferon gama/biossíntese , Interferon gama/metabolismo , Interleucina-2/metabolismo , Leucócitos Mononucleares , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento Transformadores beta/imunologia , Proteína Smad7/biossíntese , Proteína Smad7/genética , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/imunologia , Fator de Crescimento Transformador beta/administração & dosagem , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/uso terapêuticoRESUMO
IL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to investigate the impact of IL-15 on the de novo generation and function of regulatory T cells in humans. Our data indicate that IL-15 does not counteract, but rather promotes the effect of TGF-beta on the de novo generation of regulatory T cells (Treg). Thus, in the presence of TGF-beta, IL-15 enhanced the acquisition of regulatory functions by CD4(+)CD25(-) T cells stimulated by anti-CD3 and anti-CD28 Abs. In contrast, IL-15 impaired the functions of Tregs by acting on effector CD4 and CD8 T cells. Accordingly, in the presence of IL-15, proliferation and IFN-gamma production by peripheral CD4 and CD8 T cells could not be efficiently inhibited by Tregs. IL-15-induced resistance of effector T cells to Tregs resulted from activation of the PI3K signaling pathway but did not involve the rescue of effector T cells from apoptosis. Altogether, these data point to the ambiguous role of IL-15 in the control of Treg functions. This dual role may be instrumental to mount rapid but transient proinflammatory immune responses against pathogens but may become deleterious in situations associated with protracted IL-15 over-expression.