ASCA Positivity Research Articles

The Correlation between New Serological Markers and Disease Phenotype and Activation in Inflammatory Bowel Disease.

Background: The aim of the study is to assess the correlation between a new antibody panel that is developed against glycans on Crohn's disease (CD) and ulcerative colitis (UC) differentiative diagnosis and disease properties. Methods: In the study, 137 CD and 122 UC patients and 90 controls were included. Anti-saccharomyces cerevisiae IgG (ASCA), anti-laminaribioside IgG (ALCA), anti-chitobioside IgA (ACCA), and anti-mannobioside IgG (AMCA) were tested in serum. Results: While at least 1 of the other 3 serological markers was positive in 89% of ASCA-positive patients, at least 1 of the other 3 serological markers was positive in 77% of ASCA-negative patients. Positivity ratio for a single anticarbohydrate was ALCA 18 (22%), ACCA 5 (12%), and AMCA 16 (23%). A significant correlation was found between ASCA positivity (P<0.001) in operated patients and between ASCA, ALCA, and ACCA positivity (P<0.05) in patients with stricturing and fistulizing CD. According to the ROC analysis, ASCA was found to have the highest area under the curve (0.70-0.82) (correlation coefficient interval 95%). A significant correlation was found between ASCA, ALCA, and ACCA positivity and high serum antibody levels and disease activation (P<0.05). Conclusion: ASCA, ALCA, and ACCA were found to be correlated with the disease complication and activation in CD. ASCA and ALCA were determined as the best markers in the differentiation between CD and UC.

CLINICAL FEATURES AND OUTCOMES OF PAEDIATRIC PATIENTS WITH ISOLATED COLONIC CROHN’S DISEASE: A MULTICENTRE STUDY FROM THE PAEDIATRIC IBD PORTO GROUP OF ESPGHAN

Abstract BACKGROUND Adult studies suggest that patients with isolated colonic Crohn’s disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-cecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. METHODS Retrospective data was collected through the Porto IBD group of ESPGHAN on paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to 1st flare, hospital admissions, initiation of anti-TNFa drug, stricture and surgery. RESULTS Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P&amp;lt;0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of ASCA and pANCA positivity significantly differed between the groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3-82.4%), as was the response to oral steroids (70.4-76.5%) in the three groups. While times to 1st flare and admission were similar between groups, patients with L1 were commenced on anti-TNFa earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2. CONCLUSIONS Significant differences are observed in the clinical presentation and outcomes of paediatric patients with L2, compared to patients with L1 and UC.

P294 Clinic features and the prognosis of colonic Crohn’s disease

Abstract Background In this study, we aimed to investigate the prognosis of colonic Crohn’s disease (CD) and to compare colonic CD with ileocolonic CD. Methods This study included 63 patients with colonic CD who were followed at least 1 year. The same number of patients with ileocolonic CD whose age of diagnosis and sex were similar to colonic CD patients were included in the study. Data about demographics, serological, clinic characteristics, medical treatment, surgical treatment requirements and complications during follow-up were obtained retrospectively from patient files. Results The files of 1289 CD patients who were followed up at a clinic of inflammatory bowel disease of Cerrahpaşa School of Medicine were scanned. There were 63 patients with colonic CD. Control group was formed as it was noted in the Methods section. The rate of patients who smoked was lower in colonic CD (47.6% vs. 65%, p = 0.048). ASCA positivity was higher in patients with ileocolonic CD (80% vs. 33.4%, p = 0.027). At the time of diagnosis, 87.3% of colonic CD patients and 65% of ileocolonic CD patients had inflammatory phenotype (p = 0.003). During follow-up, stenosis and penetrating disease development were more common in patients with ileocolonic disease (46% vs. 15.8%, p = 0.001). The rate of abdominal surgery was lower in colonic CD (11% vs. 38%, p = 0.001). Hospitalisation rate was less in colonic CD than ileocolonic CD (36.5% vs. 57%, p = 0.02). In colonic CD, use of azatioprine was less than ileocolonic CD and the number of patients treated with oral mesalazine monotheraphy is higher than ileocolonic CD. Endoscopic remission was higher in colonic CD (%61 vs. %28, p = 0.001). Conclusion The results of our study showed that colonic CD has different phenotype characteristics, treatment response and laboratory features than ileocolonic Crohn’s disease. Colonic CD has a lower penetrating and/or stenosing phenotype rate than ileocolonic CD. Surgery and hospitalisation were less common in patients with colonic Crohn’s disease. In addition, patients with colonic CD have a higher endoscopic remission rate. For these reasons, we conclude that colonic Crohn’s disease has a better prognosis than ileocolonic Crohn’s disease.

Pancreatic Autoantibodies Against CUZD1 and GP2 Are Associated with Distinct Clinical Phenotypes of Crohn's Disease.

Inflammatory bowel disease (IBD) is characterized by a broad spectrum of clinical phenotypes with different outcomes. In the last decades, several IBD-associated autoantibodies have been identified and investigated for their diagnostic relevance. Autoantibodies against the pancreatic glycoproteins (PAB) CUB and zona pellucida-like domains-containing protein 1 (CUZD1), and glycoprotein 2 (GP2) have been demonstrated to possess high specificity for the diagnosis of IBD. Although several studies have shown significant interrelations of anti-GP2 positivity with disease phenotype, associations of clinical phenotypes with anti-CUZD1 are still unknown. The aim was to identify the association of clinical phenotypes with anti-CUZD1 and anti-GP2 in a well-defined German IBD cohort. Patients with IBD (224 patients with Crohn's disease and 136 patients with ulcerative colitis), who were tested for anti-GP2 and anti-CUZD1 immunoglobulin G and immunoglobulin A by indirect immunofluorescence on transfected cells between 2005 and 2013, were included. Serotype and specified phenotypic data were collected in retrospect and statistically analyzed. Both anti-GP2 (P < 0.001) and anti-CUZD1 (P < 0.001) were significantly more prevalent in patients with Crohn's disease than in ulcerative colitis. PAB positivity was associated with ileocolonic disease (P = 0.002), perianal disease (P = 0.011), immunosuppressive treatment (P = 0.036), and ASCA positivity (P = 0.036). Anti-CUZD1 positivity was associated with ileocolonic (P = 0.016) and perianal disease (P = 0.002), whereas anti-GP2 positivity was positively associated with stricturing behavior (P = 0.016). We found distinct clinical phenotypes to be associated with PAB positivity. Therefore, determination of PABs and their subgroup analysis might identify patients with complicated disease behavior. However, the clinical relevance of our findings should be further evaluated in prospective cohorts.

Antineutrophil cytoplasmic antibodies in bile are associated with disease activity in primary sclerosing cholangitis

Objective.Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology. The role of antineutrophil cytoplasmic antibodies (ANCAs) in the serum of patients with PSC remains unclear. We hypothesized that ANCA may be detectable in bile, potentially providing diagnostic and prognostic information. Methods.Serum and bile were prospectively collected during endoscopic retrograde cholangiography (ERC) in 72 patients with PSC and other non-PSC obstructive biliary diseases. ANCA measurements were performed by indirect immunofluorescence (IIF). Results.Immunoglobulin G (IgG) ANCA was detected significantly more often in the bile of PSC patients (15/39; 38%) than without (2/33; 6%) (p = 0.001). IgG ANCA in bile was associated with a ten times higher risk of PSC (p = 0.005). In addition, IgG ANCA positivity in bile was associated with the presence of dominant strictures (p = 0.03), cholangiographic severity (p = 0.004), number of ERC (p = 0.01) and interventions performed (p = 0.03). However, IgG ANCA in bile did not correlate with transplantation, cholangiocarcinoma or death. No association was observed between ANCA positivity in sera and ANA and ASCA positivity in sera or bile with the above-mentioned clinical features. Conclusions.The presence of ANCA in the bile of patients with PSC is a novel finding and highly suggestive of PSC. Biliary IgG ANCA correlates with the severity of bile duct strictures and the ensuing number of ERCs and interventions. Therefore, a positive ANCA status in bile may serve as a diagnostic and prognostic marker of the disease progression and biliary complications.

Is Pyloric Gland Metaplasia in Ileal Pouch Biopsies a Marker for Crohn’s Disease?

Approximately 5-10 % of ulcerative colitis (UC) patients who undergo ileal pouch-anal anastomosis (IPAA) will develop postoperative complications such as refractory pouchitis or a change in diagnosis to Crohn's disease (CD). Serological markers and histologic aspects of the pouch such as pyloric gland metaplasia (PGM) have been associated with a risk for these complications. Twenty-eight IPAA patients with either CD of the pouch or chronic pouchitis (cases) and 36 IPAA controls who experienced a normal postoperative course were originally consented. Of these 64 subjects, 22 cases and 17 controls had histopathologic and serologic data available and were subsequently enrolled. Demographic and clinical data were entered into a database, blood analyzed for serological markers (Prometheus Labs, San Diego, CA) and biopsies of the pouch and the afferent limb reviewed by two GI pathologists. Of the cases, 55 % (12/22) had evidence of PGM in their pouch and/or small bowel biopsies, as compared to 12 % (2/17) of the controls (p = 0.006). Of 13 subjects with CD, 77 % (10/13) were found to have PGM versus subjects with chronic pouchitis in which 22 % (2/9) were found to have PGM (p = 0.03). There was a trend of ASCA positivity (both IgG and IgA, p = 0.20) and of higher ASCA titer levels (p = 0.07) with postoperative complications. This study suggests that the presence of ileal pouch PGM is associated with postoperative complications and favors a diagnosis of CD over UC with chronic pouchitis.

Anti-neutrophil cytoplasmic antibodies in bile are associated with disease activity in primary sclerosing cholangitis

Objective. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology. The role of antineutrophil cytoplasmic antibodies (ANCAs) in the serum of patients with PSC remains unclear. We hypothesized that ANCA may be detectable in bile, potentially providing diagnostic and prognostic information. Methods. Serum and bile were prospectively collected during endoscopic retrograde cholangiography (ERC) in 72 patients with PSC and other nonPSC obstructive biliary diseases. ANCA measurements were performed by indirect immunofluorescence (IIF). Results. Immunoglobulin G (IgG) ANCA was detected significantly more often in the bile of PSC patients (15/39; 38%) than without (2/33; 6%) (p = 0.001). IgG ANCA in bile was associated with a ten times higher risk of PSC (p = 0.005). In addition, IgG ANCA positivity in bile was associated with the presence of dominant strictures (p = 0.03), cholangiographic severity (p = 0.004), number of ERC (p = 0.01) and interventions performed (p = 0.03). However, IgG ANCA in bile did not correlate with transplantation, cholangiocarcinoma or death. No association was observed between ANCA positivity in sera and ANA and ASCA positivity in sera or bile with the above-mentioned clinical features. Conclusions. The presence of ANCA in the bile of patients with PSC is a novel finding and highly suggestive of PSC. Biliary IgG ANCA correlates with the severity of bile duct strictures and the ensuing number of ERCs and interventions. Therefore, a positive ANCA status in bile may serve as a diagnostic and prognostic marker of the disease progression and biliary complications.

Association of deficiency for mannan-binding lectin with anti-mannan antibodies in Crohnʼs disease: A family study

Antibodies against mannan, a component of the yeast Saccharomyces cerevisiae cell wall, are more frequently found in Crohn's disease (CD) patients with low levels of mannan-binding lectin (MBL). MBL concentration depends on genetic polymorphisms. The aim of this study was to evaluate whether low MBL is related to ASCA production in healthy family members of CD patients. ASCA and MBL concentrations in sera from patients (n=52), and their 158 healthy relatives were measured by enzyme-linked immunosorbent assay (ELISA). Genetic MBL variants were determined by DNA sequencing. Thirty-five (67%) patients were ASCA-positive. Twenty-six (74%) of the 35 ASCA-positive patients had low MBL levels (<500 ng/mL), whereas only 4 (24%) of the 17 ASCA-negative patients had low values for MBL (P=0.001). ASCA were found in 38 (24%) family members. Twenty-three (50%) of 46 family members with low values for MBL were ASCA-positive compared to 15 (13%) of 112 family members with normal values for MBL (P<0.0001). ASCA were found in 33 of 104 (32%) family members of ASCA-positive patients and in 5 family members (9%) of ASCA-negative patients (P=0.002). Relatives with mutations leading to MBL deficiency had significantly more frequent ASCA than relatives without these mutations (P=0.018). MBL deficiency is associated with ASCA positivity not only in patients with CD, but also in their relatives. An impaired innate immune system defined by low MBL serum concentrations may lead to an increased reactivity of the specific immune system to mannan antigens, and therefore facilitate the generation of ASCA.

ASCA Positivity Independently Predicts Oral Crohn's Disease in a Large Early‐onset IBD Population

ASCA Positivity Independently Predicts Oral Crohn's Disease in a Large Early‐onset IBD Population

INFLAMMATORY BOWEL DISEASE SEROLOGIC MARKERS IN CHILDREN; CORRELATION WITH CLINICAL FINDINGS: A REPORT BY THE PEDIATRIC IBD COLLABORATIVE GROUP

Introduction: Several serologic markers including ASCA, anti-OmpC, and pANCA characterize patients with Crohn disease (CD). Aim: To determine whether these markers are found more commonly in different sub-groups of pediatric CD patients and whether they correlate with clinical course. Methods: Data were obtained from the prospective observational registry of the Pediatric IBD Collaborative Research Group. Results: One hundred and forty six patients with CD had complete data available for study. 61 (42%) were ASCA positive, 23 were pANCA positive (16%) and 22 were anti-OmpC positive (15%). Four patients (2.7%) were ASCA/ANCA positive, 14 children (9.6%) were ASCA/OmpC positive, and one child (0.7%) was positive for all three. Children who were ASCA positive were more likely to be >10 years (95.1% versus 78.8%, p = 0.006) and have disease in the terminal ileum (90.2% versus 71.8% p = 0.007). Children who were ASCA negative were more likely to have left sided colonic disease (72.9% versus 27.1%, p = 0.031). Thirteen children were identified with perianal fistulae and none of them were pANCA positive. All children who were anti-OmpC positive while being ASCA negative (n = 7) had CD involving the ascending and transverse colon. 90% of ASCA-/pANCA+ patients had left-sided colon disease, while 25% ASCA+/pANCA+ had left-sided colon disease (p = 0.021). There was no difference in race, gender, disease severity at diagnosis, or response to subsequent therapy. ASCA positivity did not predict the use of infliximab therapy or surgical intervention in the first year post-diagnosis. Conclusions: ASCA positive children with CD are more likely to be >10 years old and to have disease in the terminal ileum, while those ASCA negative are more likely to have left sided colonic disease. The presence or absence of ASCA was not helpful in predicting clinical course.

Anti-Saccharomyces cerevisiaeantibody titers are stable over time in Crohn’s patients and are not inducible in murine models of colitis

To investigate ASCA production over time in CD and murine colitis in order to further our understanding of their etiology. Sixty-six CD patients were compared to ulcerative colitis (UC) and irritable bowel syndrome patients with respect to ASCA production as measured by ELISA. ASCA IgG or IgA positivity as well as change in titers over a period of up to 3 years (Delta IgG/A) was correlated with clinical parameters such as CD activity index (CDAI) and C-reactive protein levels (CRP). Moreover, two murine models of colitis (DSS and IL-10 knock out) were compared to control animals with respect to ASCA titers after oral yeast exposure. ASCA IgG and IgA titers are stable over time in CD and non-CD patients. Fistular disease was associated with a higher rate of ASCA IgA positivity (P = 0.014). Ileal disease was found to have a significant influence on the Delta IgG of ASCA (P = 0.032). There was no correlation found between ASCA positivity or Delta IgG/A and clinical parameters of CD: CDAI and CRP. In mice, neither healthy animals nor animals with DSS-induced or spontaneous colitis exhibited a marked increase in ASCA titers after high-dose yeast exposure. On the other hand, mice immunized intraperitoneally with mannan plus adjuvant showed a marked and significant increase in ASCA titers compared to adjuvant-only immunized controls (P = 0.014). The propensity to produce ASCA in a subgroup of CD patients is largely genetically predetermined as evidenced by their stability and lack of correlation with clinical disease activity parameters. Furthermore, in animal models of colitis, mere oral exposure of mice to yeast does not lead to the induction of marked ASCA titers irrespective of concomitant colonic inflammation. Hence, environment may play only a minor role in inducing ASCA.

Genetic variants of the mannan-binding lectin are associated with immune reactivity to mannans in Crohn’s disease

Some patients with Crohn's disease (CD) develop antibodies against mannan, a component of the yeast Saccharomyces cerevisiae cell wall. Mannan-binding lectin (MBL), a component of the innate immune system, can bind to S. cerevisiae . MBL concentration depends on genetic polymorphisms. The aim of this study was to evaluate whether low MBL contributes to anti-S. cerevisiae antibody (ASCA) production. ASCA and MBL concentrations in sera from patients with CD (n = 74), ulcerative colitis (UC) (n = 22), and healthy controls (n = 32) were measured by an enzyme-linked immunosorbent assay (ELISA). Genetic MBL variants were determined from 58 CD patients, 18 UC patients, and 47 controls by DNA sequencing. Lymphocytes were tested for proliferative response after stimulation with mannan. ASCA were found in 47% of the patients with CD and in 0% of the controls. More ASCA-positive patients (52%) had low serum MBL concentrations compared with ASCA-negative patients (4%) (P < 0.0001). T-cell proliferation in response to mannan stimulation was observed in ASCA-positive patients and could be inhibited by the addition of MBL. These patients had significantly lower MBL serum concentrations than patients whose lymphocytes did not proliferate on mannan stimulation (P < 0.0001). Homozygous or compound heterozygous MBL mutations in the exon 1 and promoter occurred in 12 patients with cellular or humoral immune reactivity to mannan as compared with only 1 nonreactive patient (P < 0.0001). A subgroup of CD patients is characterized by ASCA positivity, T-cell proliferation on mannan stimulation, and mutations in the MBL gene that result in MBL deficiency. Thus, we propose that enhanced mannan exposure stimulates specific immune responses in a subgroup of CD patients with genetically determined low MBL concentrations. This enhanced exposure contributes to the generation of ASCA.

ASCA positivity in African Americans with Crohn’s disease is highly sensitive and specific for ileal involvement

ASCA positivity in African Americans with Crohn's disease is highly sensitive and specific for ileal involvement

TNF genotypes, asca positivity and clinical phenotypes in hispanics with IBD

Estudiar el valor de la carga viral para predecir la persistencia y/o la progresión en LSIL.Estudio prospectivo. Todos los casos diagnosticados como LSIL en el año 2006, y seguidos a los 6, 12 y 24 meses después del diagnóstico.Citología líquida (ThinPrep®, Hologic, Malborough, MA, EE. UU.) para realizar el estudio citológico. Test de captura de híbridos (HCII-HR, Quiagen, Hilden, Alemania), utilizando el test para determinar la presencia de VPH de alto riesgo.De los 102 casos, 87 fueron HPV positivos (85,3%). La persistencia o progresión se observó en el 54% de los casos en el primer control, en el 42,4% en el segundo control y en el 33,3% en el tercer control. No se demostró lesión en el seguimiento en el 46% de los casos en el primer control, en el 57% de los casos en el segundo control y en el 66,7% de los casos en el tercer control. Diecinueve casos progresaron a HSIL: 11 detectados en el primer control, 6 en el segundo y 2 en el tercero. La sensibilidad para HSIL nunca superó el 89%, con una especificidad siempre menor del 40%.La determinación de la carga viral mediante HC2 en LSIL no es útil para predecir su comportamiento.To study the HPV viral load (VL) in the prediction of the persistence and/or progression in LSIL cases.Prospective study. 102 consecutive cases diagnosed as LSIL in 2006 with follow-ups at 6, 12 and 24 months subsequent to diagnosis.Liquid based cytology (ThinPrep®, Hologic, Malborough, MA, USA), for the cytological study. Hybrid Captute II Test (HCII-HR, Quiagen, Hilden, Germany), for the determination of the presence or absence of High-Risk HPV.87 of the 102 cases studied were HR-HPV positive (85.3%). The presence or progression was detected in 54%, 42% and 33.35% of the cases in the first, second and third controls respectively. No lesion was demonstrated in 46%, 57% and 66.7% of the cases at first, second and third controls respectively. 19 cases progressed to HSIL; 11 of which were detected on the first control, 6 on the second and 2 on the third. The sensitivity of the VL for detecting HSIL never exceeded 89%, with a specificity always inferior to 40%.The VL determined by the HC2 method is not a useful indicator of prognosis in the follow-up of LSIL cases.

IGA serum antibody reactivity with I2, a novel Crohn's disease marker: anti-I2 level is independent from ASCA and ANCA levels, even though IGA ASCA positivity is correlated with anti-I2 positivity

IGA serum antibody reactivity with I2, a novel Crohn's disease marker: anti-I2 level is independent from ASCA and ANCA levels, even though IGA ASCA positivity is correlated with anti-I2 positivity