RESUMO
Vertebral artery laceration/dissection (VALD) resulting in fatal subarachnoid hemorrhage (SAH) is a rare, but well-known phenomenon encountered in the forensic setting. Delayed ruptures are exceptionally rare, and pose several challenges to the forensic pathologist. In this paper we present a case of a 47-year-old male who collapsed suddenly following recent complaints of a headache and a reported seizure. He had a reported history of potential head trauma that occurred several days prior. Attempts at resuscitation were unsuccessful, and an autopsy examination was ordered. Computer tomography (CT), autopsy, histological and ancillary studies were performed. External examination showed mild, healing trauma to the head and upper limbs, and pre-autopsy CT demonstrated a SAH. Examination of the brain showed basally oriented SAH, and there was a laceration of the left vertebral artery. Histological examination demonstrated a delayed rupture, and there was no significant blood vessel abnormality. Molecular testing was negative for collagen vascular disorders. Delayed rupture of the vertebral arteries following head trauma is rare. The presence of remote and/or mild trauma may be difficult to establish at autopsy, and it is important to identify underlying aortopathies. Several autopsy techniques and ancillary studies should be performed in these cases.
Assuntos
Lacerações/patologia , Ruptura/patologia , Hemorragia Subaracnoídea Traumática/patologia , Artéria Vertebral/lesões , Acidentes por Quedas , Contusões/patologia , Morte Súbita/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Crânio/lesões , Crânio/patologia , Hemorragia Subaracnoídea Traumática/diagnóstico por imagem , Músculo Temporal/lesões , Músculo Temporal/patologia , Fatores de Tempo , Artéria Vertebral/patologiaRESUMO
BACKGROUND: Pancreatic autoantibodies (PAB) targeting GP2 and CUZD1 are Crohn's disease (CrD)-markers. The clinical significance of anti-GP2 antibodies has been assessed, but that of anti-CUZD1 remains elusive. The aim of the study was to assess the clinical utility of anti-CUZD1/anti-GP2 by novel cell-based indirect immunofluorescence (IIF) assays in CrD. METHODS: A total of 212 CrD and 249 UC patients followed up at a London IBD centre were investigated to simultaneously detect PABs, anti-GP2 and anti-CUZD1 by IIF using primate pancreatic tissue, and HEK293 over-expressing CUZD1 or GP2. RESULTS: Overall, 88 (41.5%) CrDs compared to 26 (10.4%) UCs (p<0.001) tested positive for IgA and/or IgG anti-GP2 and/or anti-CUZD1 antibodies, while ASCA were found in 67.5% CrDs versus 19.2% UCs (p<0.0001); ASCA and/or PAB (anti-GP2 or anti-CUZD1) were detected in 76% CrD versus 34% UC patients. IgG anti-GP2 antibodies were less prevalent in L2 phenotype (p=0.002) and more prevalent in patients with stricturing disease (p=0.0418), even when a higher cut-off (≥1000 RU) was used (p=0.0396). Also, anti-GP2 IgG positive CrD patients had younger age of disease onset. IgA and/or IgG ASCA and anti-GP2 IgG antibody positive CrDs had younger onset of disease (p<0.0001), were more likely to have both ileal and colonic disease (p<0.0001) and had more stricturing (p<0.0001) than seronegative patients. Clinical correlates were not found for anti-CUZD1 positivity. CONCLUSIONS: PAB testing increases ASCA's serological sensitivity for CrD. Anti-GP2 detection, in isolation or in combination with ASCA, stratify CrD patients who phenotypically are characterised by a much younger onset of disease, extensive and stricturing behaviour.
Assuntos
Anticorpos/sangue , Autoanticorpos/sangue , Doença de Crohn/diagnóstico , Glicoproteínas de Membrana/imunologia , Proteínas de Membrana/imunologia , Adulto , Biomarcadores/sangue , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/sangue , Feminino , Células HEK293 , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Fenótipo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Saccharomyces cerevisiae/imunologiaRESUMO
BACKGROUND: A link between measles virus and Crohn's disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry. METHODS: The BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins. Antibody responses to measles/human mimics were tested by an in-house ELISA using serum samples from 50 patients with CD, 50 with ulcerative colitis (UC), and 38 matched healthy controls (HCs). RESULTS: We identified 15 sets of significant (>70%) local amino acid homologies from two measles antigens, hemagglutinin-neuraminidase and fusion-glycoprotein, and ten human intestinal proteins. Reactivity to at least one measles 15-meric mimicking peptide was present in 27 out of 50 (54%) of patients with CD, 24 out of 50 (48%) with UC (CD versus UC, p = 0.68), and 13 out of 38 (34.2%) HCs (CD versus HC, p = 0.08). Double reactivity to at least one measles/human pair was present in four out of 50 (8%) patients with CD, three out of 50 (6%) with UC (p = 0.99), and in three out of 38 (7.9%) HCs (p >0.05 for all). Titration experiments yielded different extinction curves for anti-measles and anti-human intestinal double-reactive antibodies. Epitope prediction algorithms and three-dimensional modeling provided bioinformatic confirmation for the observed antigenicity of the main measles virus epitopic regions. CONCLUSIONS: Measles sequences mimicking intestinal proteins are frequent targets of antibody responses in patients with CD, but this reactivity lacks disease specificity and does not initiate cross-reactive responses to intestinal mimics. We conclude that there is no involvement of measles/human molecular mimicry in the etiopathogenesis of CD.
Assuntos
Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Vírus do Sarampo/imunologia , Adulto , Idoso , Antígenos Virais/análise , Estudos de Casos e Controles , Biologia Computacional , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND AIM: 25-Hydroxyvitamin D [25(OH)D] has an important role in fibrosis progression and inflammatory response in patients with various etiologies of chronic liver disease. However, its influence on autoimmune hepatitis (AIH) has not been investigated. We evaluated the association of serum 25(OH)D levels with clinical, biochemical and histological features and response to therapy in AIH. MATERIALS AND METHODS: Serum 25(OH)D levels were quantified in 68 therapy naïve AIH patients and 34 healthy controls. RESULTS: Mean serum 25(OH)D levels were significantly lower in AIH compared to healthy controls (16.8 ± 9.2 vs. 35.7 ± 13.6, p < 0.0001). Low levels of 25(OH)D (<30 µg/L) were independently associated with advance fibrosis and severe interface hepatitis in AIH patients [p = 0.014; odds ratio (OR) 0.12, 95% confidence interval (CI) 0.02-0.65 and p = 0.020; OR 0.17, 95% CI 0.04-0.76, respectively]. Severe 25(OH)D deficiency (<10 µg/L) was associated with advance fibrosis, severe interface hepatitis, low platelet counts and sampling time in a univariate analysis. Only interface hepatitis and fibrosis scores were independently associated with 25(OH)D deficiency in a multiple regression analysis (p = 0.005; OR 0.12, 95% CI 0.03-0.53 and p = 0.022; OR 0.15, 95% CI 0.03-0.75, respectively). Mean serum 25(OH)D levels were lower in non-responders compared to responders (9.2 ± 4.8 vs. 17.1 ± 9.4, p = 0.015), and 25(OH)D deficiency was more commonly observed in non-responders than the responders (80 vs. 43%, p = 0.036). CONCLUSIONS: Low 25(OH)D levels are associated with advance fibrosis and severe inflammation in AIH. Our study suggests that vitamin D may be a potential biomarker that predicts response to therapy and histological features in AIH.
Assuntos
Calcifediol/sangue , Hepatite Autoimune/sangue , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Deficiência de Vitamina D/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Previous studies reported associations between specific alleles of non-HLA immunoregulatory genes and higher fatigue scores in patients with primary biliary cirrhosis (PBC). AIM: To study the relationship between variables of health-related quality of life (HRQoL) and single nucleotide polymorphisms of TRAF1-C5, a member of the tumor necrosis factor receptor family. PATIENTS AND METHODS: TRAF1-C5 gene polymorphisms, rs2900180 and rs3761847, were analysed in 120 Caucasian PBCs. The HRQoL was assessed with SF-36, PBC-40, and PBC-27 questionnaires. RESULTS: We found a negative association between TT genotype of rs2900180 and SF-36's domains vitality (P < 0.05), mental health (P < 0.05), and mental component summary score (P < 0.05). GG homozygotes of rs3761847 had lower vitality (P < 0.05), mental health (P < 0.05), mental component summary score (P < 0.05) and impairment of social functioning (P < 0.01). Allelic analysis has shown that T allele of rs2900180 and G allele of rs3761847 related to SF-36's vitality (P < 0.05 and P < 0.01), social functioning (P < 0.05 and P < 0.05), mental health (P < 0.01 and P < 0.05), and mental component summary score (P < 0.01 and P < 0.05), respectively. Genotyping and allelic analysis did not reveal correlation with PBC-40 and PBC-27 domains. CONCLUSION: The association between rs2900180 and rs3761847 polymorphisms and HRQoL variables indicates that TRAF1 is involved in the induction of impaired QoL in PBC.
Assuntos
Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/psicologia , Polimorfismo de Nucleotídeo Único , Qualidade de Vida/psicologia , Fator 1 Associado a Receptor de TNF/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Predisposição Genética para Doença , Homozigoto , Humanos , Relações Interpessoais , Cirrose Hepática Biliar/etnologia , Cirrose Hepática Biliar/imunologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , População BrancaRESUMO
BACKGROUND AND AIM: Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC). MATERIAL AND METHODS: To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months. RESULTS: At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child). CONCLUSION: The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Hemocromatose/imunologia , Mitocôndrias/imunologia , Adulto , Especificidade de Anticorpos/imunologia , Feminino , Hemocromatose/diagnóstico , Hemocromatose/cirurgia , Humanos , Imunoglobulina G/imunologia , Recém-Nascido , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/imunologia , Masculino , Mucosa Bucal/patologiaRESUMO
Twin studies are powerful tools to discriminate whether a complex disease is due to genetic or environmental factors. High concordance rates among monozygotic (MZ) twins support genetic factors being predominantly involved, whilst low rates are suggestive of environmental factors. Twin studies have often been utilised in the study of systemic and organ specific autoimmune diseases. As an example, type I diabetes mellitus has been investigated to establish that that disease is largely affected by genetic factors, compared to rheumatoid arthritis or scleroderma, which have a weaker genetic association. However, large twin studies are scarce or virtually non-existent in other autoimmune diseases which have been limited to few sets of twins and individual case reports. In addition to the study of the genetic and environmental contributions to disease, it is likely that twin studies will also provide data in regards to the clinical course of disease, as well as risk for development in related individuals. More importantly, genome-wide association studies have thus far reported genomic variants that only account for a minority of autoimmunity cases, and cannot explain disease discordance in MZ twins. Future research is therefore encouraged not only in the analysis of twins with autoimmune disease, but also in regards to epigenetic factors or rare variants that may be discovered with next-generation sequencing. This review will examine the literature surrounding twin studies in autoimmune disease including discussions of genetics and gender.
Assuntos
Doenças Autoimunes/genética , Doenças Autoimunes/etiologia , Meio Ambiente , Feminino , Humanos , Masculino , Fatores Sexuais , Estudos em Gêmeos como Assunto , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genéticaRESUMO
BACKGROUND: Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH) is eminently a paediatric disease. CASE PRESENTATION: We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA) in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1) showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF), and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. CONCLUSION: This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.
Assuntos
Anticorpos Anti-Idiotípicos/sangue , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Cirrose Hepática Biliar/imunologia , Mitocôndrias Hepáticas/imunologia , Azatioprina/uso terapêutico , Pré-Escolar , Feminino , Glucocorticoides/uso terapêutico , Hepatite Autoimune/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Prednisolona/uso terapêutico , Resultado do TratamentoRESUMO
Primary biliary cirrhosis (PBC) is a cholestatic liver disease of autoimmune origin, characterised by the destruction of small intrahepatic bile ducts. The disease has an unpredictable clinical course but may progress to fibrosis and cirrhosis. The diagnostic hallmark of PBC is the presence of disease-specific antimitochondrial antibodies (AMA), which are pathognomonic for the development of PBC. The disease overwhelmingly affects females, with some cases of male PBC being reported. The reasons underlying the low incidence of males with PBC are largely unknown. Epidemiological studies estimate that approximately 7-11% of PBC patients are males. There does not appear to be any histological, serological, or biochemical differences between male and female PBC, although the symptomatology may differ, with males being at higher risk of life-threatening complications such as gastrointestinal bleeding and hepatoma. Studies on X chromosome and sex hormones are of interest when studying the low preponderance of PBC in males; however, these studies are far from conclusive. This paper will critically analyze the literature surrounding PBC in males.
Assuntos
Cirrose Hepática Biliar/etiologia , Feminino , Humanos , Cirrose Hepática Biliar/diagnóstico , Cirrose Hepática Biliar/epidemiologia , Masculino , Fatores SexuaisRESUMO
Why zymogen glycoprotein 2 (GP2), the Crohn's disease (CD)-specific pancreatic autoantigen, is the major target of humoral autoimmunity in inflammatory bowel diseases (IBD) is uknown. Recent evidence demonstrates that GP2 is also present on the apical surface of microfold (M) intestinal cells. As the colon lacks GP2-rich M cells, we assumed that patients with colonic CD are seronegative for anti-GP2. Anti-GP2 antibodies were tested in 225 CDs, including 45 patients with colonic location (L2), 45 with terminal ileum (L1) and 135 with ileocolonic involvement; 225 patients with ulcerative colitis (UC) were also tested. Anti-GP2 reactivity was detected in 59 (26.2%) CDs and 15 (6.7%) UCs (P < 0.001). Only 5 CDs with L2 had anti-GP2 antibodies, compared to 54/180 (30.0%, P = 0.0128) of the CDs with L1 and L3. Anti-GP2 antibody positive CD patients had higher ASCA titres compared to seronegative cases. Amongst the 128 CD patients with previous surgical intervention, 45 (35.0%) were anti-GP2 antibody positive compared to 14/97 (14.0%) without surgical (P < 0.001). Our data support the assumption that ileal inflammation is required for the development of anti-GP2 antibodies in CD, and suggest that the intestine rather than the pancreatic juice is the antigenic source required for the initiation of anti-GP2 antibodies.
Assuntos
Autoanticorpos/imunologia , Doença de Crohn/imunologia , Proteínas Ligadas por GPI/imunologia , Ileíte/imunologia , Glicoproteínas de Membrana/imunologia , Adulto , Autoantígenos/imunologia , Colite Ulcerativa/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Inflamação/imunologia , Doenças Inflamatórias Intestinais/imunologia , Masculino , Pessoa de Meia-Idade , Pâncreas/imunologiaRESUMO
Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients.
Assuntos
Hepatite Autoimune/epidemiologia , Cirrose Hepática Biliar/epidemiologia , Fumar/efeitos adversos , Progressão da Doença , Hepatite Autoimune/imunologia , Hepatite Autoimune/fisiopatologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/imunologia , Cirrose Hepática/fisiopatologia , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/fisiopatologia , Fatores de RiscoRESUMO
Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the autoimmune destruction of the small intrahepatic bile ducts. The disease has an unpredictable clinical course, but may progress to fibrosis and cirrhosis. Although medical treatment with urseodeoxycholic acid is largely successful, some patients may progress to liver failure requiring liver transplantation. PBC is characterised by the presence of disease specific anti-mitochondrial (AMA) antibodies, which are pathognomonic for PBC development. The disease demonstrates an overwhelming female preponderance and virtually all women with PBC present in middle age. The reasons for this are unknown; however several environmental and immunological factors may be involved. As the immune systems ages, it become less self tolerant, and mounts a weaker response to pathogens, possibly leading to cross reactivity or molecular mimicry. Some individuals display immunological changes which encourage the development of autoimmune disease. Risk factors implicated in PBC include recurrent urinary tract infection in females, as well as an increased prevalence of reproductive complications. These risk factors may work in concert with and possibly even accelerate, immune system ageing, contributing to PBC development. This review will examine the changes that occur in the immune system with ageing, paying particular attention to those changes which contribute to the development of autoimmune disease with increasing age. The review also discusses risk factors which may account for the increased female predominance of PBC, such as recurrent UTI and oestrogens.
RESUMO
Natural killer T (NKT) cells are a distinct lineage of T cells which express both the T cell receptor (TCR) and natural killer (NK) cell markers. Invariant NKT (iNKT) cells bear an invariant TCR and recognize a small variety of glycolipid antigens presented by CD1d (nonclassical MHC-I). CD1d-restricted iNKT cells are regulators of immune responses and produce cytokines that may be proinflammatory (such as interferon-gamma (IFN-γ)) or anti-inflammatory (such as IL-4). iNKT cells also appear to play a role in B cell regulation and antibody production. Alpha-galactosylceramide (α-GalCer), a derivative of the marine sponge, is a potent stimulator of iNKT cells and has been proposed as a therapeutic iNKT cell activator. Invariant NKT cells have been implicated in the development and perpetuation of several autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus (SLE). Animal models of SLE have shown abnormalities in iNKT cells numbers and function, and an inverse correlation between the frequency of NKT cells and IgG levels has also been observed. The role of iNKT cells in autoimmune liver disease (AiLD) has not been extensively studied. This review discusses the current data with regard to iNKT cells function in AiLD, in addition to providing an overview of iNKT cells function in other autoimmune conditions and animal models. We also discuss data regarding the immunomodulatory effects of vitamin D on iNKT cells, which may serve as a potential therapeutic target, given that deficiencies in vitamin D have been reported in various autoimmune disorders.
Assuntos
Colangite Esclerosante/imunologia , Hepatite Autoimune/imunologia , Cirrose Hepática Biliar/imunologia , Células T Matadoras Naturais/imunologia , Vitamina D/fisiologia , Animais , Linfócitos B/imunologia , Humanos , Imunidade Inata , Células Supressoras Mieloides/imunologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/fisiologia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T Reguladores/imunologiaRESUMO
BACKGROUND: We developed a new IgA and IgG anti-MZGP2 antibody ELISAs based on recombinant isoform-4 of human zymogen granule protein-2 (GP2), which is the major autoantigen of Crohn's disease (CrD)-specific pancreatic autoantibodies and assessed their clinical relevance in the largest inflammatory bowel disease (IBD) cohort tested to date. METHODS: 832 sera were studied, including 617 consecutive IBD patients from 323 CrD and 294 ulcerative colitis (UC) follow-up in a tertiary centre, and 112 pathological and 103 normal controls. RESULTS: Sensitivity of IgA anti-MZGP2 for CrD in the IBD population was 15% and specificity was 98% (95, 99), while the sensitivity and specificity of IgG anti-MZGP2 were 27% and 97%. IgA and IgG anti-MZGP2 combined testing led to a sensitivity of 31% and a specificity of 96%. Positivity for either ASCA (IgA or IgG) or anti-MZGP2 (IgA or IgG) showed a sensitivity of 75% (70, 80) and a specificity of 84% (79, 89). IgA anti-MZGP2 antibodies were more prevalent in CrD patients with early disease onset (p=0.011). Also, anti-MZGP2 positive patients more frequently had extensive disease with ileal involvement. Patients with longer disease duration were more likely to have IgG anti-MZGP2 antibodies. CONCLUSIONS: Our novel ELISA confirms the high specificity of anti-MZGP2 antibodies for CrD and their association with disease severity phenotypes.
Assuntos
Autoanticorpos/imunologia , Doença de Crohn/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas Ligadas por GPI/imunologia , Pâncreas/imunologia , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Doença de Crohn/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are demyelinating disorders affecting the central nervous system. An autoimmune aetiology has been proposed for both. ADEM principally affects adolescents following acute infection by a variety of pathogens and has also been reported to occur following vaccination. ADEM typically resolves following medical treatment, whereas MS follows a more relapsing and remitting course. The pathogenesis of MS remains unclear, but it is thought that a combination of infectious and non-infectious environmental factors and host genetics act synergistically to cause disease. A variety of viruses, including Epstein Barr virus, cytomegalovirus, herpes simplex virus and varicella zoster virus, have been implicated as possible infectious triggers. The similar clinical and pathological presentation of ADEM and MS presents a diagnostic challenge for distinguishing ADEM from a first episode of MS. Some cases of ADEM progress to MS for reasons that are not currently clear. This review examines the evidence for infectious agents as triggers for ADEM progressing to MS and suggests potential methods that may facilitate identification of infectious agents that may be responsible for the pathogenesis of ADEM to MS.
Assuntos
Encefalomielite Aguda Disseminada/epidemiologia , Esclerose Múltipla/epidemiologia , Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Animais , Autoanticorpos/imunologia , Encefalomielite Aguda Disseminada/etiologia , Encefalomielite Aguda Disseminada/imunologia , Humanos , Mimetismo Molecular , Esclerose Múltipla/etiologia , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologiaRESUMO
Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role of Escherichia coli (E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens and E. coli mimics have been clearly demonstrated, adding support to the notion that E. coli is a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving the E. coli/PBC association was the lack of reliable E. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developed E. coli-infected animal model of PBC.
RESUMO
Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research.
Assuntos
Doenças Autoimunes/imunologia , Autoimunidade , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Animais , Anticorpos Antibacterianos/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/microbiologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Medição de Risco , Fatores de RiscoRESUMO
Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease serologically characterized by the presence of high-titer antimitochondrial antibodies and, histologically by chronic nonsuppurative cholangitis and granulomata. The aetiology of the disease remains elusive, although genetic, epigenetic, environmental, and infectious factors have been considered important for the induction of the disease in genetically prone individuals. The disease shows a striking female predominance and becomes clinically overt at the fourth to sixth decade. These characteristics have prompted investigators to consider infections that predominate in women at these ages as the likely candidates for triggering the disease. Recurrent urinary tract infections due to Escherichia coli were the first infections to be considered pathogenetically relevant. Over the years, several other microorganisms have been linked to the pathogenesis of PBC owing to epidemiological, immunological, microbiological, or experimental findings in animal models. Recent studies have provided data supporting the pathogenic role of Novosphingobium aromaticivorans and betaretroviruses. Several reports have linked other organisms to the induction of the disease and/or the maintenance of the auto-aggressive responses that are perpetuated over the course of the disease. This review highlights the findings of the most recent studies investigating the link between infections and PBC. We also discuss the close interplay of the infectious agents with other environmental and genetic factors, which may explain the multifaceted nature of this puzzling disease.
RESUMO
The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation.
Assuntos
Doenças Autoimunes/imunologia , Hepatopatias/imunologia , Vitamina D/metabolismo , Proliferação de Células , Citocinas/metabolismo , Genótipo , Humanos , Imunomodulação , Esclerose Múltipla/metabolismo , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Linfócitos T/fisiologia , Vitamina D/análogos & derivados , Deficiência de Vitamina D/metabolismo , Proteína de Ligação a Vitamina D/genéticaRESUMO
p38 mitogen activated protein kinase (p38 MAPK) signaling plays a major role in the modulation of immune-mediated inflammatory responses and therefore has been linked with several autoimmune diseases. The extent of the involvement of p38 MAPK in the pathogenesis of autoimmune blistering diseases has started to emerge, but whether it pays a critical role is a matter of debate. The activity of p38 MAPK has been studied in great detail during the loss of keratinocyte cell-cell adhesions and the development of pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These diseases are characterised by autoantibodies targeting desmogleins (Dsg). Whether autoantibody-antigen interactions can trigger signaling pathways (such as p38 MAPK) that are tightly linked to the secretion of inflammatory mediators which may perpetuate inflammation and tissue damage in pemphigus remains unclear. Yet, the ability of p38 MAPK inhibitors to block activation of the proapoptotic proteinase caspase-3 suggests that the induction of apoptosis may be a consequence of p38 MAPK activation during acantholysis in PV. This review discusses the current evidence for the role of p38 MAPK in the pathogenesis of pemphigus. We will also present data relating to the targeting of these cascades as a means of therapeutic intervention.