RESUMO
OBJECTIVES: To evaluate the prevalence and meaning of antineutrophil cytoplasmic antibodies (ANCA) positivity in a cohort of IgG4-related disease (IgG4-RD). METHODS: We identified patients with ANCA determination from a retrospective cohort of 69 patients with IgG4-RD. ANCA were measured by indirect immunofluorescence microscopy (IIF) and/or proteinase 3 (PR3)-ANCA and MPO-ANCA by ELISA. IIF patterns were classified as perinuclear (P-ANCA), cytoplasmic (C-ANCA) and atypical (X-ANCA). We compared the ANCA-positive vs the ANCA-negative IgG4-RD group. RESULTS: Out of 69 patients, 31 IgG4-RD patients had an ANCA determination. Four patients with concomitant systemic autoimmune diseases were excluded. We found positive ANCA by IIF in 14 (56%) of 25 patients tested. The most common IIF pattern was C-ANCA in eight (57.1%), followed by dual C-ANCA/X-ANCA in four (28.6%) and P-ANCA and dual C-ANCA/P-ANCA in one each (7.1%). Of the 20 patients with ANCA determination by both IIF and ELISA, four have positive ANCA by ELISA (three for MPO-ANCA and one for PR3-ANCA). Of the two patients with only ELISA determination, one was positive for MPO-ANCA. The prevalence of ANCA positivity by ELISA was 22.7% (5 out of 22 patients). ANCA was more frequent in the Mikulizc/systemic phenotype (42.9%) compared with other phenotypes (P = 0.04). ANCA-positive IgG4-RD patients had more frequently lymph node and kidney involvement, high IgG1 levels and erythrocyte sedimentation rate, and positive antinuclear antibodies. CONCLUSION: ANCA are found in a significant number of patients with IgG4-RD and differed from the ANCA-negative group in terms of clinical and serological features.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Doença Relacionada a Imunoglobulina G4/imunologia , Nefropatias/imunologia , Linfonodos/imunologia , Mieloblastina/imunologia , Peroxidase/imunologia , Adulto , Idoso , Doenças da Aorta/imunologia , Doenças Biliares/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Doenças do Aparelho Lacrimal/imunologia , Hepatopatias/imunologia , Masculino , Microscopia de Fluorescência , Pessoa de Meia-Idade , Mieloblastina/metabolismo , Pancreatopatias/imunologia , Peroxidase/metabolismo , Espaço Retroperitoneal , Estudos Retrospectivos , Doenças das Glândulas Salivares/imunologiaRESUMO
Identifying an infection may be difficult in the ED. Neutrophilic leukocytosis is often used in the diagnosis of infection despite its lack of specificity in situations of stress. Our objective was to study the value of each parameter of the WBC count, in particular eosinopenia, to diagnose bacterial infections in the ED. We conducted a retrospective and observational study over a period of 6 months. All patients with one of the following diagnoses were eligible: pneumonia (9.9%), pyelonephritis (26.2%), prostatitis (8.4%), appendicitis (26.2%), cholecystitis (8.4%), and diverticular sigmoiditis (5%). A total of 466 infected patients were included for statistical analysis, and a control group of 466 uninfected patients was randomly selected in the same period of time. All leukocyte count parameters were significantly modified (p < 0.001) in the infected group compared with the control group. Neutrophils and total leukocytes remain the two most suitable parameters for the diagnosis of infections in the ED. Eosinopenia represented the most efficient parameter of the WBC count for the diagnosis of urinary and biliary tract infections. Deep eosinopenia presented a specificity of 94% for the diagnosis of infection. Any modification of the WBC count associated with an elevation of CRP (> 40 mg/L) or fever (> 38.5 °C) showed a high specificity for the diagnosis of infection. A careful analysis of the WBC count remains a valuable tool for the diagnosis of infection in the ED.
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Infecções Bacterianas/diagnóstico , Serviço Hospitalar de Emergência , Eosinófilos/patologia , Contagem de Leucócitos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/imunologia , Doenças Biliares/imunologia , Doenças Biliares/microbiologia , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Sepse/diagnóstico , Sepse/imunologia , Sepse/microbiologia , Índice de Gravidade de Doença , Infecções Urinárias/diagnósticoRESUMO
No disponible
Assuntos
Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Doenças Biliares/imunologia , Imunodeficiência de Variável Comum/complicações , Gastroenteropatias/imunologia , Hepatopatias/imunologia , EndoscopiaRESUMO
The liver is a vital organ with distinctive anatomy, histology and heterogeneous cell populations. These characteristics are of particular importance in maintaining immune homeostasis within the liver microenvironments, notably the biliary tree. Cholangiocytes are the first line of defense of the biliary tree against foreign substances, and are equipped to participate through various immunological pathways. Indeed, cholangiocytes protect against pathogens by TLRs-related signaling; maintain tolerance by expression of IRAK-M and PPARγ; limit immune response by inducing apoptosis of leukocytes; present antigen by expressing human leukocyte antigen molecules and costimulatory molecules; recruit leukocytes to the target site by expressing cytokines and chemokines. However, breach of tolerance in the biliary tree results in various cholangiopathies, exemplified by primary biliary cholangitis, primary sclerosing cholangitis and biliary atresia. Lessons learned from immune tolerance of the biliary tree will provide the basis for the development of effective therapeutic approaches against autoimmune biliary tract diseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Assuntos
Doenças Autoimunes/imunologia , Ductos Biliares/imunologia , Doenças Biliares/imunologia , Células Epiteliais/imunologia , Tolerância Imunológica , Animais , Apresentação de Antígeno/imunologia , Doenças Autoimunes/microbiologia , Doenças Autoimunes/prevenção & controle , Ductos Biliares/citologia , Ductos Biliares/metabolismo , Ductos Biliares/microbiologia , Doenças Biliares/microbiologia , Doenças Biliares/prevenção & controle , Células Epiteliais/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Quinases Associadas a Receptores de Interleucina-1/imunologia , Quinases Associadas a Receptores de Interleucina-1/metabolismo , PPAR gama/imunologia , PPAR gama/metabolismo , Transdução de Sinais/imunologia , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismoRESUMO
AIM: To evaluate the differences in outcomes between ABO-incompatible (ABO-I) liver transplantation (LT) and ABO-compatible (ABO-C) LT. METHODS: A systematic review and meta-analysis were performed by searching eligible articles published before No-vember 28, 2016 on MEDLINE (PubMed), EMBASE, and Cochrane databases. The primary endpoints were graft survival, patient survival, and ABO-I-related complications. RESULTS: Twenty-one retrospective observational studies with a total of 8247 patients were included in this meta-analysis. Pooled results of patient survival for ABO-I LT were comparable to those for ABO-C LT. However, ABO-I LT showed a poorer graft survival than ABO-C LT (1-year: OR = 0.66, 95%CI: 0.57-0.76, P < 0.001; 3-year: OR = 0.74, 95% CI 0.64-0.85, P < 0.001; 5-yearr: OR =0.75, 95%CI: 0.66-0.86, P < 0.001). Furthermore, ABO-I LT was associated with more incidences of antibody-mediated rejection (OR = 74.21, 95%CI: 16.32- 337.45, P < 0.001), chronic rejection (OR =2.28, 95%CI: 1.00-5.22, P = 0.05), cytomegalovirus infection (OR = 2.64, 95%CI: 1.63-4.29, P < 0.001), overall biliary complication (OR = 1.52, 95%CI: 1.01-2.28, P = 0.04), and hepatic artery complication (OR = 4.17, 95%CI: 2.26-7.67, P < 0.001) than ABO-C LT. In subgroup analyses, ABO-I LT and ABO-C LT showed a comparable graft survival in pediatric patients and those using rituximab, and ABO-I LT showed an increased acute cellular rejection in cases involving deceased donor grafts. CONCLUSION: Although patient survival in ABO-I LT was comparable to that in ABO-C LT, ABO-I LT was inferior to ABO-C LT in graft survival and several complications. Graft survival of ABO-I LT could be comparable to that of ABO-C LT in pediatric patients and those using rituximab.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Doença Hepática Terminal/mortalidade , Rejeição de Enxerto/sangue , Transplante de Fígado/efeitos adversos , Adulto , Fatores Etários , Aloenxertos/imunologia , Doenças Biliares/epidemiologia , Doenças Biliares/imunologia , Criança , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Incidência , Transplante de Fígado/métodos , Estudos Observacionais como Assunto , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
This study aimed to elucidate the impact of epithelial regenerative responses and immune cell infiltration on biliary complications after liver transplantation. Bile duct (BD) damage after cold storage was quantified by a BD damage score and correlated with patient outcome in 41 patients. Bacterial infiltration was determined by fluorescence in situ hybridization (FISH). BD samples were analyzed by immunohistochemistry for E-cadherin, cytokeratin, CD56, CD14, CD4, CD8, and double-immunofluorescence for cytokine production and by messenger RNA (mRNA) microarray. Increased mRNA levels of adherens junctions (P < 0.01) were detected in damaged BDs from patients without complications compared with damaged BDs from patients with biliary complications. Immunohistochemistry showed increased expression of E-cadherin and cytokeratin in BDs without biliary complications (P = 0.03; P = 0.047). FISH analysis demonstrated translocation of bacteria in BDs. However, mRNA analysis suggested an enhanced immune response in BDs without biliary complications (P < 0.01). Regarding immune cell infiltration, CD4+ and CD8+ cells were significantly increased in patients without complications compared with those with complications (P = 0.02; P = 0.01). In conclusion, following BD damage during cold storage, we hypothesize that the functional regenerative capacity of biliary epithelium and enhanced local adaptive immune cell infiltration are crucial for BD recovery. Such molecular immunological BD analyses therefore could help to predict biliary complications in cases of "major" epithelial damage after cold storage.Liver Transplantation 23 1422-1432 2017 AASLD.
Assuntos
Ductos Biliares/fisiologia , Doenças Biliares/imunologia , Transplante de Fígado/efeitos adversos , Linfócitos/imunologia , Complicações Pós-Operatórias/imunologia , Regeneração/imunologia , Imunidade Adaptativa , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Ductos Biliares/microbiologia , Doenças Biliares/epidemiologia , Isquemia Fria/efeitos adversos , Citocinas/metabolismo , Doença Hepática Terminal , Epitélio/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Incidência , Fígado/imunologia , Fígado/patologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , RNA Mensageiro/metabolismoRESUMO
IgG4-related hepatobiliary diseases are part of a multiorgan fibroinflammatory condition termed IgG4-related disease, and include IgG4-related sclerosing cholangitis (IgG4-SC) and IgG4-related hepatopathy. These diseases can present with biliary strictures and/or mass lesions, making them difficult to differentiate from primary sclerosing cholangitis (PSC) or other hepatobiliary malignancies. Diagnosis is based on a combination of clinical, biochemical, radiological and histological findings. However, a gold standard diagnostic test is lacking, warranting the identification of more specific disease markers. Novel assays - such as the serum IgG4:IgG1 ratio and IgG4:IgG RNA ratio (which distinguish IgG4-SC from PSC with high serum IgG4 levels), and plasmablast expansion to recognize IgG4-SC with normal serum IgG4 levels - require further validation. Steroids and other immunosuppressive therapies can lead to clinical and radiological improvement when given in the inflammatory phase of the disease, but evidence for the efficacy of treatment regimens is limited. Progressive fibrosclerotic disease, liver cirrhosis and an increased risk of malignancy are now recognized outcomes. Insights into the genetic and immunological features of the disease have increased over the past decade, with an emphasis on HLAs, T cells, circulating memory B cells and plasmablasts, chemokine-mediated trafficking, as well as the role of the innate immune system.
Assuntos
Doenças Biliares/diagnóstico , Colangite Esclerosante/diagnóstico , Hepatite Autoimune/diagnóstico , Paraproteinemias/diagnóstico , Corticosteroides/uso terapêutico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Linfócitos B/imunologia , Doenças Biliares/tratamento farmacológico , Doenças Biliares/imunologia , Linfócitos T CD4-Positivos/imunologia , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/tratamento farmacológico , Diagnóstico Diferencial , Previsões , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Humanos , Imunidade Inata , Memória Imunológica/imunologia , Imunossupressores/uso terapêutico , Pancreatite/diagnóstico , Pancreatite/tratamento farmacológico , Pancreatite/imunologia , Paraproteinemias/tratamento farmacológico , Paraproteinemias/imunologia , Recidiva , Fatores de Risco , Terminologia como Assunto , Resultado do TratamentoRESUMO
Increasing evidence points to the contribution of the intestinal microbiome as a potentially key determinant in the initiation and/or progression of hepatobiliary disease. While current understanding of this dynamic is incomplete, exciting insights are continually being made and more are expected given the developments in molecular and high-throughput omics techniques. In this brief review, we provide a practical and updated synopsis of the interaction of the intestinal microbiome with the liver and its downstream impact on the initiation, progression and complications of hepatobiliary disease.
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Doenças Biliares/microbiologia , Sistema Biliar/microbiologia , Microbioma Gastrointestinal , Saúde , Intestinos/microbiologia , Hepatopatias/microbiologia , Fígado/microbiologia , Microbiota , Animais , Sistema Biliar/imunologia , Doenças Biliares/imunologia , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/imunologia , Fígado/imunologia , Hepatopatias/imunologia , Transdução de Sinais/imunologiaAssuntos
Gastroenteropatias/diagnóstico , Gastroenteropatias/imunologia , Trato Gastrointestinal/imunologia , Imunoglobulina G/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Biliares/diagnóstico , Doenças Biliares/imunologia , Gastroenteropatias/terapia , Trato Gastrointestinal/patologia , Humanos , Imunoglobulina G/metabolismo , Imunossupressores/uso terapêutico , Hepatopatias/diagnóstico , Hepatopatias/imunologia , Doença de Mikulicz/diagnóstico , Doença de Mikulicz/imunologia , Pancreatite/diagnóstico , Pancreatite/imunologiaRESUMO
CONTEXT: Immunoglobulin G4 (IgG4)-related disease is a systemic fibroinflammatory disease capable of affecting virtually any organ. Although the pancreas and hepatobiliary system are commonly affected, involvement of the tubular gut is unusual. The pancreatic manifestations of this disease (autoimmune pancreatitis) often mimic pancreatic carcinoma, whereas the hepatobiliary manifestations are mistaken for cholangiocarcinoma or primary sclerosing cholangitis. The characteristic histologic features include a dense lymphoplasmacytic infiltrate, storiform-type fibrosis, and obliterative phlebitis. An increase in IgG4(+) plasma cells and an IgG4 to IgG ratio of more than 40% are considered obligatory components of the diagnostic algorithm. OBJECTIVE: To review the challenges associated with the diagnosis of IgG4-related disease of the gastrointestinal tract. DATA SOURCES: A review of pertinent literature, along with the author's personal experience, based on institutional and consultation materials. CONCLUSION: The complete spectrum of histologic changes is seldom captured in a biopsy specimen, and thus, the histopathology findings are best interpreted within the overall clinical context. Increased IgG4(+) plasma cells are identified in a variety of benign and malignant diseases of the gastrointestinal tract.
Assuntos
Gastroenteropatias/imunologia , Trato Gastrointestinal/imunologia , Imunoglobulina G/imunologia , Plasmócitos/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Doenças Biliares/diagnóstico , Doenças Biliares/imunologia , Doenças Biliares/terapia , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Trato Gastrointestinal/patologia , Humanos , Imunoglobulina G/metabolismo , Hepatopatias/diagnóstico , Hepatopatias/imunologia , Hepatopatias/terapia , Pancreatite/diagnóstico , Pancreatite/imunologia , Pancreatite/terapia , Plasmócitos/metabolismo , Guias de Prática Clínica como AssuntoRESUMO
It is ironic that the liver, which serves a critical function in immune tolerance, itself becomes the victim of an autoimmune attack. Indeed, liver autoimmunity and the autoimmune diseases associated with both innate and adaptive responses to hepatocytes and/or cholangiocytes are models of human autoimmunity. For example, in primary biliary cirrhosis, there exists a well-defined and characteristic autoantibody and considerable homogeneity between patients. In autoimmune hepatitis, there are clinical characteristics that allow a rigorous subset definition and well-defined inflammatory infiltrates. In both cases, there are defects in a variety of immune pathways and including regulatory cells. In primary sclerosing cholangitis, with its characteristic overlap with inflammatory bowel disease, there are unique defects in innate immunity and particular important contribution of lymphoid homing to disease pathogenesis. In these diseases, as with other human autoimmune processes, there is the critical understanding that pathogenesis requires a genetic background, but is determined by environmental features, and indeed the concordance of these diseases in identical twins highlights the stochastic nature of immunopathology. Unfortunately, despite major advances in basic immunology and in immunopathology in these diseases, there remains a major void in therapy. The newer biologics that are so widely used in rheumatology, neurology, and gastroenterology have not yet seen success in autoimmune liver disease. Future efforts will depend on more rigorous molecular biology and systems analysis in order for successful application to be made to patients.
Assuntos
Doenças Autoimunes/imunologia , Doenças Biliares/imunologia , Hepatopatias/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/terapia , Doenças Biliares/diagnóstico , Doenças Biliares/epidemiologia , Doenças Biliares/terapia , Humanos , Hepatopatias/diagnóstico , Hepatopatias/epidemiologia , Hepatopatias/terapiaRESUMO
OBJECTIVES: Although most reported patients with immunoglobulin G4-related disease (IgG4-RD) are from the Far East, we aimed to identify patients suffering from IgG4-RD in our University Centre in Debrecen, Hungary. METHOD: Serum IgG4 levels were measured at 51 of our 800 patients followed up because of Sjögren's syndrome (SS) if one or more clinical signs during the disease course raised the possibility of IgG4-RD (persisting salivary gland swelling, absence of anti-Ro/SSA and anti-La/SSB antibodies in the serum, and positive salivary gland biopsy, coexistence of autoimmune pancreatitis, autoimmune hepatitis, or primary sclerosing cholangitis, persisting lymphadenopathy). Where available, histological samples of small salivary gland biopsies were revised to detect the particular features of IgG4-RD. Pathologists and surgeons were informed about the disease and asked to refer suspicious cases. RESULTS: Based on our survey, eight patients were identified with IgG4-RD. Pancreatic, salivary gland, aortic, and retroperitoneal manifestations were detected. Of the 51 patients with SS, four appeared to have IgG4-RD, but eventually one was excluded. CONCLUSIONS: Although IgG4-RD is not yet well known to physicians of Western countries, it occurs in Caucasians and probably in other races as well. Moreover, our eight cases diagnosed with IgG4-RD demonstrate a relatively large European patient population collected in a single centre. European clinicians, and especially rheumatologists, should be informed and at least certain laboratories should be prepared to investigate patient samples if the suspicion of IgG4-RD is raised. The main clinical significance of an accurate diagnosis is the extreme corticosteroid sensitivity of IgG4-RD.
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Doenças Autoimunes/diagnóstico , Doenças Biliares/diagnóstico , Imunoglobulina G/sangue , Pancreatopatias/diagnóstico , Espaço Retroperitoneal/patologia , Doenças das Glândulas Salivares/diagnóstico , Síndrome de Sjogren/diagnóstico , Adulto , Idoso , Doenças Autoimunes/imunologia , Doenças Biliares/imunologia , Feminino , Humanos , Hungria , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pancreatopatias/imunologia , Doenças das Glândulas Salivares/imunologia , Síndrome de Sjogren/imunologiaRESUMO
AIM: To investigate the pathogenesis of biliary casts after liver transplantation relative to their morphology and biochemical markers. METHODS: The microstructure of biliary casts was assessed using scanning electron microscopy and Hematoxylin and eosin staining assessed their histology. The expression levels of CD3, CD5, CD34, CD68 and CD79a in these biliary casts were evaluated immunohistochemically. RESULTS: Biliary casts differed widely in their microstructure, with some containing blood vessels positive for CD34 and collagen fibers with positive Masson staining. Large numbers of neutrophils and other inflammatory cells were present, but only on the edge of the biliary casts; although the boundaries were clear without crossover. None of the biliary casts contained T-lymphocytes, B-lymphocytes, macrophages and other inflammatory cells. CONCLUSION: The microcostructure of biliary casts differed. Bacteria and acute rejection are not clearly related to their formation.
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Ductos Biliares/imunologia , Ductos Biliares/ultraestrutura , Doenças Biliares/etiologia , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Antígenos CD/análise , Antígenos CD34/análise , Antígenos de Diferenciação Mielomonocítica/análise , Doenças Biliares/imunologia , Doenças Biliares/patologia , Biomarcadores/análise , Vasos Sanguíneos/imunologia , Vasos Sanguíneos/ultraestrutura , Complexo CD3/análise , Antígenos CD5/análise , Antígenos CD79/análise , Colágeno/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/ultraestruturaRESUMO
Cholangiocytes, or bile duct epithelia, were once thought to be the simple lining of the conduit system comprising the intra- and extrahepatic bile ducts. Growing experimental evidence demonstrated that cholangiocytes are in fact the first line of defense of the biliary system against foreign substances. Experimental advances in recent years have unveiled previously unknown roles of cholangiocytes in both innate and adaptive immune responses. Cholangiocytes can release inflammatory modulators in a regulated fashion. Moreover, they express specialized pattern-recognizing molecules that identify microbial components and activate intracellular signaling cascades leading to a variety of downstream responses. The cytokines secreted by cholangiocytes, in conjunction with the adhesion molecules expressed on their surface, play a role in recruitment, localization, and modulation of immune responses in the liver and biliary tract. Cholangiocyte survival and function is further modulated by cytokines and inflammatory mediators secreted by immune cells and cholangiocytes themselves. Because cholangiocytes act as professional APCs via expression of major histocompatibility complex antigens and secrete antimicrobial peptides in bile, their role in response to biliary infection is critical. Finally, because cholangiocytes release mediators critical to myofibroblastic differentiation of portal fibroblasts and hepatic stellate cells, cholangiocytes may be essential in the pathogenesis of biliary cirrhosis.
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Ductos Biliares/citologia , Ductos Biliares/imunologia , Epitélio/imunologia , Bile/metabolismo , Sistema Biliar/imunologia , Doenças Biliares/imunologia , Moléculas de Adesão Celular/imunologia , Citocinas/imunologia , Proteínas de Ligação ao GTP/fisiologia , Cadeias alfa de HLA-DR/fisiologia , Humanos , Imunidade Inata/fisiologia , Imunoglobulina A/fisiologia , Cirrose Hepática/fisiopatologia , Proteínas de Resistência a Myxovirus , Receptores Toll-Like/fisiologia , beta-Defensinas/fisiologiaRESUMO
Opisthorchiasis caused by Opisthorchis viverrini infection induces hepatobiliary disease (HBD)-associated cholangiocarcinoma (CCA) via a chronic inflammatory immune response. Here, we evaluated specific IgG and IgA antibodies against different fractions of O. viverrini antigen in residents from an endemic community in Northeast Thailand with varying hepatobiliary abnormalities. Crude somatic O. viverrini antigen was purified into three fractions (viz., P1, P2 and P3) by gel infiltration chromatography and these served as antigens for detection of fluke-specific IgG and IgA antibodies by enzyme-linked immunosorbent assay (ELISA). The results revealed fluke-specific IgG and IgA antibody levels-against these antigens from subjects with O. viverrini-positive HBD-higher than in subjects with O. viverrini-negative HBD. Interestingly, the rank of fluke-specific IgG (and not IgA) antibody levels against crude extract and P1 antigens was CCA>severe HBD>mild HBD>healthy individuals. Purified antigens reduced cross-reactivity with other parasites compared to the crude antigen. Multiple linear regression analysis showed that HBD status was significantly associated with the liver fluke-specific IgG antibody against purified antigens. These results suggest that purified O. viverrini-antigen improves serodiagnosis for the evaluation of opisthorchiasis-associated HBD, and may be useful in the screening of opisthorchiasis in subjects at risk of developing CCA.
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Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Opistorquíase/imunologia , Opisthorchis/imunologia , Adulto , Animais , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/imunologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/imunologia , Ductos Biliares Intra-Hepáticos/patologia , Sistema Biliar/diagnóstico por imagem , Sistema Biliar/imunologia , Sistema Biliar/patologia , Doenças Biliares/sangue , Doenças Biliares/complicações , Doenças Biliares/diagnóstico por imagem , Doenças Biliares/imunologia , Colangiocarcinoma/sangue , Colangiocarcinoma/complicações , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/imunologia , Cromatografia em Gel , Cricetinae , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Feminino , Peixes/parasitologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Modelos Lineares , Fígado/diagnóstico por imagem , Fígado/imunologia , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/complicações , Hepatopatias/diagnóstico por imagem , Hepatopatias/imunologia , Masculino , Pessoa de Meia-Idade , Opistorquíase/diagnóstico , Especificidade da Espécie , Tailândia , UltrassonografiaRESUMO
BACKGROUND: Since the discovery of Helicobacter pylori, various enterohepatic Helicobacter spices have been detected in the guts of humans and animals. Some enterohepatic Helicobacters have been associated with inflammatory bowel disease or liver disease in mice. However the association of these bacteria with human diseases remains unknown. MATERIALS AND METHODS: We collected 126 bile samples from patients with cholelithiasis, cholecystitis, gallbladder polyp, and other nonbiliary diseases. Samples were screened for the presence of enterohepatic Helicobacter spp. using cultures, nested PCR, or in situ hybridization. We tested for antibodies to H. pylori and H. hepaticus by Western blot analysis. RESULTS: Attempts at cultivation were unsuccessful. However, H. hepaticus was detected in bile samples with nested PCR whereas H. bilis was not. Helicobacter hepaticus in the bile was confirmed by in situ hybridization, but H. hepaticus from bile samples was coccoid in appearance. We detected immunoglobulin G antibodies to H. hepaticus in bile samples by Western blotting. Helicobacter hepaticus was detected in 40 (32%) of total 126 samples as H. hepaticus positive if at least one of the three methods with nested PCR, in situ, or Western blotting. Patients with cholelithiasis (41%) and cholecystitis with gastric cancer (36%) had significantly higher (p = .029) prevalence of H. hepaticus infection than samples from patients with other diseases. CONCLUSION: Helicobacter hepaticus may closely associate with diseases of the liver and biliary tract in humans.
Assuntos
Bile/microbiologia , Doenças Biliares/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter hepaticus/isolamento & purificação , Idoso , Anticorpos Antibacterianos/análise , Bile/imunologia , Doenças Biliares/imunologia , Feminino , Infecções por Helicobacter/imunologia , Helicobacter hepaticus/genética , Helicobacter hepaticus/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Bile ducts lined with biliary epithelial cells, or cholangiocytes, are the main components of the biliary system in liver. Cholangiocytes participate in the production and transport of bile substances, as well as participate in immune responses. Cholangiocytes protect against pathogens by expressing toll-like receptors and anti-microbial peptides; act as antigen-presenting cells by expressing human leukocyte antigen molecules and costimulatory molecules; recruit leukocytes to the target site by expressing adhesion molecules, cytokines, and chemokines; and induce apoptosis of leukocytes to limit the immune responses. Several cholangiopathies result from dysfunctions of the biliary system. They can broadly be divided into autoimmune, genetic, infectious, drug, and ischemic-injury-induced categories. The pathogenesis of many of these cholangiopathies is unclear and treatment is limited. Further understanding of the complexity of the biliary system is critical for medical advancements in this field.
Assuntos
Doenças Biliares/imunologia , Sistema Biliar/imunologia , Epitélio/imunologia , Fígado/imunologia , Apresentação de Antígeno/imunologia , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Apoptose/imunologia , Sistema Biliar/metabolismo , Doenças Biliares/metabolismo , Doenças Biliares/fisiopatologia , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Epitélio/metabolismo , Humanos , Imunoglobulina A Secretora/imunologia , Imunoglobulina A Secretora/metabolismo , Fígado/patologia , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismoRESUMO
Whereas autoimmune pancreatitis is an established entity characterized by high serum concentrations of IgG4, IgG4 cholangitis is a quite new entity characterized by a massive infiltration of bile ducts by IgG4 positive lymphoplasmocytic cells. IgG4 cholangitis should therefore be differentiated from primary sclerosing cholangitis based on clinics, radiological and biological markers. This paper is aimed at reviewing all new aspects of diseases associated with high levels of IgG4.