anti-Saccharomyces Cerevisiae Antibodies Status Research Articles

Predicting Outcomes in Pediatric Crohn’s Disease for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease–Ahead Program

A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.

Association of Anti-Saccharomyces cerevisiae antibodies with clinical phenotype in spondyloarthritis patients

The association between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) has been shown in many studies. More recently, with the hypothesis that increased gut inflammation is of etiopathogenic importance in the development of SpA, evaluation of anti-Saccharomyces cerevisiae antibodies (ASCA) has gained increasing relevance. To study the status and frequency of ASCA in SpA patients and the association of these biomarkers with the clinical profile. An observational study was performed including 231 SpA patients treated with biologic therapy. ASCA IgA and IgG levels were determined by micro-enzyme-linked immunosorbent assay. Our data showed an increase of ASCA IgA positivity among SpA patients. No relationship was found between ASCA status and the demographic aspects, genetic factors or clinical presentation, except for the association with IBD. Our study confirms that ASCA IgA are elevated in SpA patients. Although there was no evidence of association with a particular disease phenotype, the existence of higher ASCA levels sustains a close relationship between gut and SpA.

Variation of Gut Mucosal Microbiome With Anti-Saccharomyces cerevisiae Antibody Status in Pediatric Crohn Disease.

Crohn disease (CD) is a chronic relapsing condition possibly caused by a dysbiotic microbiome. Approximately 30% to 60% of patients with CD have anti-Saccharomyces cerevisiae antibody (ASCA), but any association with gut microbiota is unexplored. We hypothesized that ASCA positivity would predict a signature microbial status and clinical phenotype. Ileocolonic mucosal biopsies were obtained from children with CD (n = 135), and controls without inflammatory bowel disease (n = 45). Comparison was made between ASCA status, microbial diversity, and clinical characteristics. ASCA was highly specific but poorly sensitive for the diagnosis of CD. In patients with CD, ASCA positivity was associated with older age (≥10 years), ileocolonic disease, and long-term risk of surgery. Microbial alpha and beta diversity were similar in patients with CD with or without ASCA, but significantly less when compared to noninflammatory bowel disease controls. Microbial richness was similar across all 3 groups. Fourteen bacterial species were associated with ASCA-positive patients with CD and 14 species with ASCA-negative patients (P < 0.05). After using a false discovery rate correction Ruminococcus torques and bacterium Yersinia enterocolitica 61 remained significantly associated with CD ASCA positivity (P = 0.0178), whereas Enterobacter cloacae and Faecalibacterium prausnitzii were significantly associated with CD ASCA negativity (P = 0.0178 and 0.0342). ASCA-positive and ASCA-negative patients with CD have significant differences in gut microbiome composition, which could possibly be influencing the phenotype of the disease.

Serological markers in diagnosis of pediatric inflammatory bowel disease and as predictors for early tumor necrosis factor blocker therapy

Objective: To describe the prevalence of serological markers in newly diagnosed treatment-naïve pediatric inflammatory bowel disease (IBD), their utility in differentiating Crohn’s disease (CD), ulcerative colitis (UC) and symptomatic non-IBD patients and whether serological markers are associated with early TNF blocker treatment.Material and methods: Ninety-six children and adolescents <18 years, 58 with IBD and 38 symptomatic non-IBD controls were included. At diagnosis and after 1–2 years, serological antibodies (anti-Saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), flagellin expressed by Clostridial phylum (anti-CBir1), outer membrane porin of Escherichia coli (anti-OmpC), Pseudomonas fluorescens-associated sequence (anti-I2), CRP, ESR and fecal calprotectin were analyzed. The choice of treatment was made at the discretion of the treating pediatrician.Results: Of the IBD patients, 20 (36%) and 26 (47%) were positive for ASCA and pANCA compared to 3(8%), p < .01 and 10 (27%), p = .04 of the controls. Thirteen (72%) of UC patients were pANCA positive, versus 13 (35%) of CD patients (p < .01). None of the UC patients was ASCA positive versus 20 (54%) of CD patients (p < .0001). Compared to conventionally treated patients, the 18 (49%) TNF blocker treated CD patients had higher presence of ASCA (p < .01), lower presence of pANCA (p = .02) and higher levels of fecal calprotectin, CRP and ESR at diagnosis. In multivariate analyses ASCA and pANCA status, but not CRP, ESR or calprotectin, were independently associated with early TNF blocker treatment.Conclusions: ASCA and pANCA status were associated with having IBD and with early TNF blocker treatment in CD.

Anti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthritis: Prevalence and associated phenotype

ObjectiveThe aim of the study was to compare the prevalence of ASCA in spondyloarthrites (SpA) patients and to investigate the association between ASCA status and disease phenotype. MethodsWe performed a case-control study including SpA individuals fulfilling the ESSG SpA criteria. The following data were collected for analysis: gender, age, disease duration, clinical or associated features of SpA, treatments, HLAB27 and ASCA status. A control group of patients without SpA was also analyzed. ResultsA total of 235 patients with SpA and 54 control patients were studied. The median age of SpA patients (53.6% of male patients, 52.2% of HLAB27) was 46.0 [IQR 35.0–57.0] years old. Disease duration was 60.0 [IQR 24.0–156.0] months. Inflammatory bowel diseases were observed in 11% of SpA patients. ASCA positivity was significantly higher in SpA patients than in control patients (25.5% [95% CI 20.1–31.6] (IgG: 9.8%; IgA: 21.7%) vs. 7.4% [95% CI 2.1–17.9], P=0.004). Multivariate analysis revealed that ASCA positivity was associated with peripheral involvement (OR: 3.30 [1.26–8.62], P=0.015), presence of IBD (OR: 3.43 [1.15–10.20], P=0.026), past of present history of uveitis (OR: 4.36 [1.08–17.64], P=0.039) and arthritis (OR: 3.78 [1.57–9.15], P=0.003). ConclusionOur results provided evidence that SpA patients had an increased prevalence of ASCA and that ASCA positivity might be associated with a particular phenotype, notably peripheral involvement and uveitis.

FRI0461 Do the anti-saccharomyces cerevisiae antibodies (ASCA) modify the ankylosing spondylitis phenotype?

BackgroundThe anti-saccharomyces cerevisiae antibodies (ASCA) are serum markers in inflammatory bowel disease (IBD) either Crohn’s disease (CD) or ulcerative colitis (UC), which are present in almost 50% patients with CD....

Meta‐analysis: serological markers and the risk of acute and chronic pouchitis

Serological markers such as anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) may be associated with pouchitis after ileal pouch-anal anastomosis (IPAA). To perform a systematic review with meta-analysis of studies evaluating the association of ANCA and ASCA status with risk of acute and chronic pouchitis after IPAA. We searched multiple databases (upto September 2012) for studies reporting ANCA and/or ASCA status along with risk of acute or chronic pouchitis after IPAA in adults with ulcerative colitis (UC). We abstracted odds ratio (OR) or raw data from the individual studies to calculate summary OR estimates with 95% CIs using random-effects model. Eight studies reporting 184 cases of acute pouchitis and six studies reporting 151 cases of chronic pouchitis were included. The odds of chronic pouchitis were 76% higher in ANCA-positive patients than ANCA-negative (six studies; OR: 1.76; 95% CI: 1.19-2.61; P < 0.01). ASCA-positivity was not associated with the risk of chronic pouchitis (three studies; OR: 0.89; 95% CI: 0.49-1.59; P = 0.68). Neither ANCA (eight studies; OR: 1.54; 95% CI: 0.79-3.02; P = 0.21) nor ASCA-positivity (two studies; OR: 1.28; 95% CI: 0.25-6.54; P = 0.77) were associated with the risk of acute pouchitis. The risk of chronic pouchitis after IPAA is higher in ANCA-positive patients, but the risk of acute pouchitis is unaffected by ANCA status. ASCA status was not associated with the risk of acute or chronic pouchitis. This information may be used to counsel UC patients regarding their risk of pouchitis after IPAA.

Anti-Saccharomyces cerevisiae Antibodies Associate with Phenotypes and Higher Risk for Surgery in Crohn’s Disease: A Meta-Analysis

Recent studies suggested that anti-Saccharomyces cerevisiae antibody (ASCA) status was associated with diagnostic findings, stratified classification phenotypes, disease activity and clinical course of Crohn's disease (CD). However, the relationship between ASCA status and phenotypes of CD remains controversial in these studies. The purpose of this study was to evaluate whether ASCA status is associated with the phenotypes and the risk of surgery in diverse populations in CD. We conducted a meta-analysis of studies assessing the association of ASCA status with phenotypes and risk of surgery in CD. Three independent reviewers undertook data extraction. We pooled odds ratios separately for the cohort and case-control studies. We identified ten cohort studies (n = 2,365) and 14 case-control studies (n = 1,887) that investigated the association of ASCA status with phenotypes and risk of surgery in CD. The meta-analysis of the cohort studies showed significant association between the ASCA-positive status and higher risk of early-onset age (OR 2.25, 95 % CI 1.41-3.57, P < 0.001), ileal involvement disease (1.70, 1.05-2.77, P = 0.03), complicated disease behavior (2.09, 1.71-2.57, P < 0.001), perianal disease (1.49, 1.14-1.94, P = 0.004), and risk for surgery (1.61, 1.29-2.01, P < 0.001). Meta-analysis of the case-control studies also showed a significantly higher risk in ileal involvement disease (1.77, 1.25-2.49, P = 0.001), complicated disease behavior (2.13, 1.70-2.68, P < 0.001), perianal disease (1.96, 1.38-2.78, P < 0.001), and risk for surgery (1.71, 1.17-2.49, P = 0.005), except for the early-onset age (1.16, 0.80-1.69, P = 0.44). This meta-analysis indicated that positive ASCA status is a risk factor for early-onset age, ileal involvement, complicated behavior, perianal disease and requirement for surgery in CD.

Anti‐Saccharomyces cerevisiae Antibodies Status Is Associated with Oral Involvement and Disease Severity in Crohn Disease

To determine anti-Saccharomyces cerevisiae antibodies (ASCA) status and its relation to disease phenotype in patients with inflammatory bowel disease (IBD). A total of 301 Scottish patients with early-onset IBD-197 Crohn disease (CD), 76 ulcerative colitis (UC), 28 indeterminate colitis (IC)-and 78 healthy control individuals were studied. ASCA status (IgA, IgG) was determined by enzyme-linked immunosorbent assay. ASCA status was then analyzed in relation to CD phenotype. Patients with CD had a higher prevalence of ASCA than patients with UC and healthy controls: 82/197 versus 12/76, odds ratio (OR) 3.80 (1.93-7.50) and 82/197 versus 6/78, OR 8.56 (3.55-20.62), respectively. Univariate analysis showed that positive ASCA status was associated with oral CD (17/25 vs 59/153, OR 3.39 [1.38-8.34]), perianal CD (39/77 vs 38/108, OR 1.89 [1.04-3.44]) and the presence of granulomata (63/132 vs 15/52, OR 2.25 [1.13-4.48]) and also with markers of disease severity: raised C-reactive protein (44/90 vs 12/49, OR 2.95[1.36-6.37]), hypoalbuminemia (44/85 vs 20/74, OR 2.28[1.19-4.37]), and surgery (27/49 vs 54/147, OR 2.11 [1.10-4.06]). From multivariate analysis, the presence of oral disease (adjusted P = 0.001, OR 22.22 [3.41-142.86]) and hypoalbuminemia (adjusted P = 0.01, OR 4.78 [1.40-16.39]) was found to be independently associated with ASCA status. No association was demonstrated between ASCA and IBD candidate genes. Patients with CD had a higher prevalence of ASCA than did other patients with IBD. ASCA status described patients with CD who had a specific phenotype, showing an association with markers of disease severity and oral CD involvement.

The Role of Serologic Markers in Identifying Infliximab Response in Ulcerative Colitis

Purpose: The definition of colitis is evolving from the traditional two-disease model – ulcerative colitis (UC) and Crohn's disease (CD) – towards an immuno-inflammatory spectrum of disease. Molecular diagnostic tools, including serological markers for perinuclear anti-neutrophil cytoplasmic antibody (pANCA) which suggests more of a UC phenotype, as well as both anti-Saccharomyces cerevisiae antibody (ASCA) and outer membrane porin of Escherichia coli (OmpC) suggest more of a CD phenotype, hold promise for stratifying differing patterns of colitis. Furthermore, anti-CBir1 antibody helps distinguish between UC and CD in pANCA positive patients. While infliximab (IFX) is approved for the treatment of both CD and moderate to severe UC, approximately one third of UC patients do not respond. The primary objective is to assess whether serologic markers identify a subset of patients with UC who are likely to respond to infliximab therapy. Methods: We retrospectively reviewed those patients with UC who were treated with IFX from January 2002 to September 2006 and also were tested for serologic markers including ASCA, pANCA and OmpC. The Ulcerative Colitis Disease Activity Index (UCDAI) was calculated on all patients in a prospective manner. All patients included in the study underwent mucosal evaluation both prior to and following IFX treatment. The primary endpoint was response to infliximab, as defined by a 3-point improvement in the UCDAI. These patients were then stratified by pANCA and ASCA status. Regression analysis was performed to determine the predictive value of the serologies. Results: We analyzed a total of 11 patients, and 10/11 (91%) were pANCA positive. There were 7 patients who responded to IFX, with a with a mean decrease of UCDAI of 3.83 (range 3–5, P < 0.001). Of the responders, 42.9% (3/7) were ASCA (IgG and IgA) positive and 85.7% (6/7) were pANCA positive. Of the 6 patients who were pANCA positive, 33.3% (2/6) were also ASCA positive and 66.7% (4/6) were either ASCA and/or OmpC positive. The 4 patients who were IFX non-responders had no significant change in UCDAI (mean change in UCDAI of 0.5, P= 0.182) and all were only positive for pANCA with high titers. The combination of ASCA and OmpC together showed a trend towards infliximab response. Conclusion: Serologies in colitis patients suggesting a Crohn's phenotype – either ASCA positive alone or pANCA positive in combination with ASCA or OmpC – may identify an immunologically vulnerable subset who are likely to respond to anti-TNF therapy. Further study in a larger group of colitis patients with the addition of other markers, including anti-CBir1, to stratify therapeutic responses, is warranted.

ASCA positivity is associated with increased risk for early surgery in Crohn’s disease

Purpose: Serum markers have been used as tools in the diagnosis of inflammatory bowel diseases (Crohn's disease and ulcerative colitis) including anti-Saccharomyces cerevisiae antibodies (ASCA), neutrophil-specific nuclear autoantibodies (pANCA), and antibodies to outer membrane protein C of Escherichia coli (OmpC). It has been suggested that ASCA status correlates with aggressive phenotype in Crohn's disease (CD) including early age of onset, fibrostenosis, and internal fistulae. We performed a case-control study to evaluate the role of ASCA as a risk factor for early surgery in CD.

Anti-saccharomyces cerevisiae antibodies (ASCA) in Crohn's disease: Stability over time and correlation with clinical characteristics

Background and Aims:ASCA is a serologic marker that may help in the diagnosis of Crohn's disease(CD) with a sensitivity of 60-70%. The value of serial ASCA measurements in CD is unclear. We assessed the stability of ASCA in CD patients followed prospectively with repeated measures during a 1 year period. The relationship of ASCA with various clinical characteristics was also evaluated. Methods: 78 CD patients in remission had ASCA measured every 3 months up to 1 year or earlier if they relapsed. ASCA was measured using the QUANTA Lite kit (lgA,IgG) (Inova diagnostics, San Diego). Serum values were interpreted using cut-offs provided by the manufacturer ( 25 =positive). ASCA was also measured at 1 timepoint in 70 non-lBD healthy controls. Relapse was defined as a CDAI> 150 with a 70 point increase from baseline The association of ASCA with: age, age at diagnosis, gender, smoking status, disease site and duration, extraintestinal symptoms and immunosuppressant use was assessed by multivariate analylsis. Results: At baseline, 45 patients were ASCA + compared to 8 ASCA + controls (p = <0.001). 2 patients and 3 controls were ASCA equivocal. The sensitivity and specificity of ASCA for CD was 60% and 88% respectively (excluding equivocals). 44 patients remained in remission at 1 year and 34 relapsed. In non-relapsers with 4 or 5 measurements (n = 42), 83% (95% C1, 70-92%) maintained the same ASCA (+ or -) throughout the year. In relapsers, with 4 or 5 measurements (n= 14), 64 % (95%C1, 38-86%) remained unchanged. Overall, ASCA status remained unchanged in 79% (n =44)(95%C1,66-88%) of patients with 4 or 5 measurements. In patients with equivocal ASCA (n = 19) at some timepoint, 47%(95%CI,2769%) remained equivocal, 37% (95%CI,18-60%) became negative and 16% (95%CI,4-37%) changed to positive at next measurement. No relapsers who were ASCA at baseline remission converted to AgCA + at relapse. Also, mean lgA and IgG levels decreased from the remission state to relapse (IgA, 37 to 29, p= 0.04 ; lgG, 45 to 34, p =0.01 ). When assessing clinical factors an association between ASCA and older age at diagnosis (p=0.03) was found. Conclusion: This study demonstrates that ASCA is a stable marker when measured over a 1 year period and only few patients switch ASCA status regardless of disease activity.Therefore,repeatmg measurements in view of increasing the yield of a positive result is likely of little benefit. Also, ASCA was associated with older age at diagnosis.

Detection of anti- Saccharomyces cerevisiae antibodies in Crohn's disease: is it reliable diagnostic and prognostic marker?

Background. In the past few years, serologic markers have been proposed in inflammatory bowel disease. Anti-Saccharomyces cerevisiae antibodies showed high specificity for Crohn's disease. A prognostic role for serology has also been hypothesised. Aims To evaluate anti-Saccharomyces cerevisiae antibody distribution in an unselected Italian inflammatory bowel disease population. To analyse whether anti-Saccharomyces cerevisiae antibody status (positive/negative) and/or anti-Saccharomyces cerevisiae antibody titres are associated with clinical variables and outcome measures in Crohn's disease patients. Patients and Methods. A series of 299 inflammatory bowel disease patients were evaluated; serum samples were taken and a short clinical history was recorded. anti-Saccharomyces cerevisiae antibodies IgG enzyme-linked immunosorbent assay Medilab® (Milan, Italy) kit was used in order to determine anti-Saccharomyces cerevisiae antibody status. Results. Sensitivity, specificity and likelihood ratio for positive test in the differential diagnosis of inflammatory bowel disease was 59%, 89%, 8.1, respectively. Clinical variables significantly associated with anti-Saccharomyces cerevisiae antibody status in logistic regression were found to be ileal location (p =0.01) and earlier age at diagnosis (p<0.01). Among ileal Crohn's disease patients, there was a trend in concordance between anti-Saccharomyces cerevisiae antibody titres and higher number of surgical procedures which was not statistically significant applying more complex statistics. Conclusions. In an Italian inflammatory bowel disease population, anti-Saccharomyces cerevisiae antibodies status showed characteristics similar to those previously reported. Anti-Saccharomyces cerevisiae antibody positivity is associated with ileal involvement and with earlier onset of Crohn's disease.