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1.
J Hepatol ; 59(3): 457-66, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23639483

RESUMEN

BACKGROUND & AIMS: Anti-neutrophil cytoplasmic antibodies (ANCA) are a non-uniform family of antibodies recognizing diverse components of neutrophil granulocytes. ANCA formation might be induced by protracted bacterial infections or probably reflect an abnormal immune response to commensal microorganisms. Bacterial infections are common complications in cirrhosis with high incidence of episodes caused by enteric organisms, therefore, we sought to study the presence and clinical importance of ANCA in cirrhosis. METHODS: Sera of 385 patients with cirrhosis of different etiologies were assayed for ANCA of IgG, IgA, IgA1, IgA2, and secretory IgA subtypes by indirect immunofluorescence and ELISAs. The control group comprised 202 patients with chronic liver diseases without cirrhosis and 100 healthy subjects. In cirrhosis, a 2-year follow-up, observational study was conducted to assess a possible association between the presence of ANCA and clinically significant bacterial infections. RESULTS: Prevalence of ANCA IgA was significantly higher in cirrhosis (52.2%) compared to chronic liver diseases (18.6%) or healthy controls (0%, p<0.001 for both). ANCA IgA subtyping assays revealed marked increase in the proportion of IgA2 subtype (46% of total ANCA IgA) and presence of the secretory component concurrently. Presence of ANCA IgA was associated with disease-specific clinical characteristics (Child-Pugh stage and presence of ascites, p<0.001). During a 2-year follow-up period, risk of infections was higher among patients with ANCA IgA compared to those without (41.8% vs. 23.4%, p<0.001). ANCA IgA positivity was associated with a shorter time to the first infectious complication (pLogRank <0.001) in Kaplan-Meier analysis and was identified as an independent predictor in multivariate Cox-regression analysis (HR:1.74, 95% CI: 1.18-2.56, p=0.006). CONCLUSIONS: Presence of IgA type ANCA is common in cirrhosis. Involvement of gut mucosal immune system is in center of their formation and probably reflects sustained exposure to bacterial constituents.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Infecciones Bacterianas/etiología , Infecciones Bacterianas/inmunología , Inmunoglobulina A/sangre , Cirrosis Hepática/complicaciones , Cirrosis Hepática/inmunología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/inmunología , Humanos , Inmunoglobulina A/clasificación , Cirrosis Hepática Alcohólica/complicaciones , Cirrosis Hepática Alcohólica/inmunología , Cirrosis Hepática Biliar/complicaciones , Cirrosis Hepática Biliar/inmunología , Hepatopatías/complicaciones , Hepatopatías/inmunología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo
2.
J Crohns Colitis ; 7(2): 134-41, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22504031

RESUMEN

BACKGROUND: Mannose-binding lectin (MBL) is a pattern-recognition molecule of the innate immune system and may be involved in the pathogenesis of inflammatory bowel disease (IBD). Our aim was to assess the prevalence of MBL deficiency in a cohort of patients with paediatric-onset IBD and study whether it is associated with the clinical manifestations, serum antibody formation, or genetic factors. METHODS: This prospective study included 159 paediatric patients (mean age: 14.0 years) with IBD [107 patients with Crohn disease (CD) and 52 patients with ulcerative colitis (UC)]. Furthermore, 95 controls were investigated. Serum samples were determined for MBL by enzyme-linked immunosorbent assay (ELISA) and for serologic markers [autoantibodies against Saccharomyces cerevisiae (ASCA) and perinuclear components of neutrophils (pANCA)] by indirect immunofluorescent assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The MBL serum concentration was significantly lower in IBD patients(both with CD and UC) compared to controls (IBD, p=0.007, CD, p=0.04, UC p=0.004). Prevalence of low MBL level (<500 ng/mL) was significantly higher in both CD and UC groups compared to controls (p=0.002 and p=0.006). Furthermore, low MBL level was associated with isolated ileal involvement (p=0.01) and MBL deficiency (<100 ng/mL) with male gender (p=0.004) in patients with CD. We failed to confirm any correlation between MBL deficiency and serum autoantibodies or NOD2/CARD15 variants. CONCLUSIONS: Our results suggest that low MBL associated with paediatric-onset IBD and ileal CD may be considered an additional marker of the IBD pathogenesis.


Asunto(s)
Colitis Ulcerosa/sangre , Enfermedad de Crohn/sangre , Lectina de Unión a Manosa/deficiencia , Adolescente , Adulto , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , Colitis Ulcerosa/diagnóstico , Intervalos de Confianza , Enfermedad de Crohn/diagnóstico , Femenino , Humanos , Íleon/patología , Masculino , Lectina de Unión a Manosa/sangre , Proteína Adaptadora de Señalización NOD2/sangre , Oportunidad Relativa , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales , Estadísticas no Paramétricas , Adulto Joven
3.
J Pediatr Gastroenterol Nutr ; 55(4): 429-35, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22465933

RESUMEN

BACKGROUND: Significance of pancreatic autoantibodies determined by using exocrine pancreas (PAB) and antibodies against recombinant pancreas antigen (rPAB), as well as the importance of autoantibodies against goblet cells (GAB), is not known in pediatric patients with inflammatory bowel disease (IBD). Our aim was to determine the complex analysis of PAB, rPAB, GAB, antibodies against Saccharomyces cerevisiae, and perinuclear components of neutrophils in pediatric patients with IBD. Moreover, association with NOD2/CARD15 and disease phenotype was determined. METHODS: A total of 152 pediatric patients (median age 13.9 years) with IBD (103 patients with Crohn disease [CD] and 49 patients with ulcerative colitis [UC]) and 104 controls were included. Serum autoantibodies were determined by indirect immunofluorescence assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The presence of PAB and rPAB was significantly higher in CD (34% and 35.9%) and in UC (20.4% and 24.5%) compared with pediatric control cohort (0% and 0%, P<0.0001). In addition, GAB positivity was significantly increased in patients with UC in comparison with CD and controls, respectively (UC, 12.2%; CD, 1.9%; controls, 1.9%; P=0.02). Specificity of PAB and rPAB was 100%; however, sensitivity was low. The combination of PAB and/or antibodies against Saccharomyces cerevisiae/perinuclear components of neutrophils improved the sensitivity of serological markers in CD (87.4%) and in UC (79.6%); specificities were 89.3% and 93.2%, respectively. Pancreatic autoantibodies (PAB, rPAB) and GAB were not related to clinical presentation, medical therapy, or need for surgery in CD or in UC. CONCLUSIONS: Pancreatic autoantibodies and GAB were specific for IBD, but the sensitivity was limited as well because there was lack of correlation with clinical phenotype. Combinations of these antibodies have shown increased sensitivity; therefore, it may be recommended in the diagnostic procedure of IBD.


Asunto(s)
Autoanticuerpos/sangre , Colitis Ulcerosa/diagnóstico , Enfermedad de Crohn/diagnóstico , Células Caliciformes/inmunología , Páncreas Exocrino/inmunología , Adolescente , Adulto , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Antifúngicos/sangre , Niño , Preescolar , Colitis Ulcerosa/sangre , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/sangre , Enfermedad de Crohn/inmunología , Femenino , Humanos , Masculino , Neutrófilos/inmunología , Saccharomyces cerevisiae/inmunología , Adulto Joven
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