anti-Saccharomyces Cerevisiae Antibodies Positivity Research Articles

P0176 Single-cell RNA sequencing reveals the immunological mechanisms underlying Anti-saccharomyces cerevisiae antibody positivity in both non-inflamed and inflamed mucosal tissues of IBD patients

Abstract Background Previous studies have shown anti-saccharomyces cerevisiae antibody (ASCA) positivity in inflammatory bowel disease (IBD) patients is associated with increased risk of developing IBD and poor prognosis. However, no comprehensive study has elucidated the ASCA positive-related immunological phenotype in non-inflamed and inflamed colonic mucosa and its clinical implications. Methods We collected endoscopic biopsies from 43 ulcerative colitis [28 non-inflamed sites and 43 inflamed sites] and 20 Crohn’s disease at Seoul National University Hospital. Single-cell RNA sequencing (scRNA-seq) was performed on these samples according to the ASCA positivity. First, we compared ASCA-positive and -negative samples obtained from non-lesion sites of UC patients. Second, we investigated immunologic phenotypes in inflamed mucosa based on the disease activity (remission vs active). Results We conducted scRNA-seq analysis of over 130,000 single cells from 28 biopsies obtained from non-inflamed tissues of UC patients. Substantial reduction in the frequency of type 3 innate lymphoid cells (ILC3) and expression of IL18 and IL22 in ILC3s, along with a significant decrease in tight junction-associated genes (TJP1, CLDN3, CLDN4) within epithelial cells were observed in the positive group[P <0.05]. In addition, data from positive group exhibited decreased levels of CSF2 in ILC3s, which is likely contributing to reduced M2 macrophage polarization. We performed scRNA-seq analysis of over 123,673 single cells from 63 biopsies obtained from inflamed tissues. In active inflamed status, the expression of IL-17A - a cytokine that helps maintain tight-junction barrier in the intestinal epithelium during inflammation was decreased in tissue-resident memory T cells (Tc17 TRM) [P 0.026]. In addition, ASCA positive resulted in decreased CD4 central memory T cells (CD4 TCM) [P 0.046], suggesting impaired gut barrier function and subsequent rapid response to reencountered antigens. Cytotoxic gene expression, including granzyme and perforin 1, was increased in CD8 T effector memory cells (CD8 TEM) [P<0.05] during remission, suggesting that ongoing subclinical inflammation may develop and contribute to tissue damage. Conclusion These findings suggest that Saccharomyces cerevisiae infection induces immunological changes characterized by gut barrier dysfunction, rapid responses to commensal antigens, and increased cytotoxic gene expression. Based on these findings, we believe that Saccharomyces cerevisiae may serve as a potential target for preventing disease progression in patients with IBD.

P0437 Positive anti-Saccharomyces cerevisiae antibodies do not affect clinical outcomes in pediatric patients with Crohn’s disease treated with anti-TNF therapy

Abstract Background Anti-Saccharomyces cerevisiae antibodies (ASCA) have been associated with a more aggressive Crohn’s disease (CD) phenotype. However, the effect of ASCA serology on the response to biologic therapy, specifically in children on anti-TNF therapy, is unknown. Our goal was to assess whether ASCA levels are associated with clinical outcomes in pediatric CD patients treated with anti-TNF antibodies. Methods A single center retrospective study. Demographic, clinical and laboratory data were collected from pediatric CD patients (aged 2.2-17.9 years) treated with anti-TNF therapy, who were tested for IgG ASCA levels upon diagnosis, between 2010-2023. The cut-off value for a positive ASCA result was defined as 30 EU/mL. Clinical outcomes included durability of anti-TNF therapy, corticosteroid-free survival (CSFS) at week 52 of therapy, IBD-associated hospitalizations and IBD related surgery. Results One hundred seventy-two patients with CD (69 ,39% females) with a median age at diagnosis of 13.5 (11.1-15.4) years were included. Ninety-two (52%) patients had positive ASCA (> 30 EU/mL). ASCA positivity was associated with female sex (p=0.02) and ileocolonic disease location at diagnosis (p=0.02). Sixty-six (37%) patients were treated with infliximab and 111 (63%) with adalimumab. The median time of follow-up in our cohort was 115 (65-174) weeks. Time to discontinuation of anti-TNF was comparable between patients with ASCA positive and negative levels (97.8% vs. 97.4% and 89.3% vs. 87.4% at 1 and 3 years, respectively). In addition, time to IBD-associated hospitalization and surgery were also similar. Interestingly, patients with positive ASCA achieved CSFR more often, compared to patients with ASCA negative (P=0.04). Sub-analysis of patients with high ASCA values, the top 20%, (>80 EU/mL) demonstrated significantly longer durability of anti-TNF, compared to the patients with lower ASCA levels (<80 EU/mL,p= 0.02). Conclusion ASCA positivity is not associated with worse outcomes in pediatric patients with CD treated with TNF antagonists.

ANCA and ASCA Profiles in a Moroccan Population With Inflammatory Bowel Diseases.

Diagnosing inflammatory bowel disease (IBD) is hindered by the invasive procedures required for accurate classification as Crohn's disease (CD) or ulcerative colitis (UC). As alternatives, non-invasive tests using anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-neutrophil cytoplasmic antibodies (ANCA) have gained significance. This study evaluated ANCA and ASCA antibody frequencies in IBD and their role in disease characterization in a Moroccan population. Conducted at Marrakech's Mohammed VI University Hospital from 2014 to 2018, this cross-sectional study included patients with suggestive symptoms or confirmed IBD diagnosis based on clinical, endoscopic, and histological criteria. Immunological investigations detected p-ANCA, c-ANCA, and ASCA using immunofluorescence and immunodot assays. Among 60 participants (mean age: 33.1 ± 11.75 years), the 20-30-year age group was most affected (31.67%). CD, UC, and indeterminate colitis (IC) were diagnosed in 46.67%, 45%, and 8.33% patients, respectively. Gastrointestinal symptoms were prevalent (98.3%), with ANCA+/ASCA-profile in 41% of UC patients versus 11% in CD, and ANCA-/ASCA + profile exclusive to CD (50%). ANCA positivity was significantly associated with UC, rectal syndrome, and inflammatory syndrome, whereas ASCA positivity was significantly associated with CD and König's syndrome (p < 0.05). This study highlighted demographic and phenotypic particularities of IBD in a Moroccan population. Non-invasive tests using ASCA and ANCA antibodies offer valuable alternatives to invasive procedures, facilitating personalized management strategies. Variations in ANCA and ASCA profiles provide insights into disease characterization and inform tailored treatment approaches.

Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures

Inflammatory bowel diseases (IBDs), e.g., Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. Using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq), we identified antibodies against 344,000 antimicrobial, immune, and food antigens in 497 individuals with IBD compared with 1,326 controls. IBD was characterized by 373 differentially abundant antibody responses (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD, and 28% unique to UC. Antibody reactivities against bacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenotic disease, and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitope repertoires accurately discriminated CD from controls (area under the curve [AUC]= 0.89), and similar discrimination was achieved when using only ten antibodies (AUC= 0.87). Individuals with IBD thus show a distinct antibody repertoire against selected peptides, allowing clinical stratification and discovery of immunological targets.

Anti-Saccharomyces cerevisiae antibodies (ASCA) in peptic ulcer disease with Helicobacter pylori

Anti-Saccharomyces cerevisiae antibodies (ASCA) is related to the pathogenesis of Crohn’s disease as digestive tract inflammation. But the relationship between ASCA and peptic ulcer as upper digestive tract inflammation is unknown. The aim of this study was to determine the prevalence of ASCA positivity in patients with peptic ulcer and the relationship between ASCA and Helicobacter pylori. Total 128 patients with peptic ulcer were enrolled at Nagoya university hospital from 1999 to 2005. Serum samples obtained from with all peptic ulcer patients were examined. Determination of ASCA was performed by ELISA method. All patients were confirmed H. pylori infection. 10 patients with H. pylori infection were treated with eradication therapy. Fifty-five patients of 128 were suffered from active peptic ulcer. Of 128, 38 patients were ASCA-positive. 34 patients of 38 ASCA positive patients were active ulcer and other 4 patients were ulcer-scar. ASCA positivity in active ulcer patients was more significant than that in ulcer-scar. The H. pylori–positive patients were 78. Thirty patients were ASCA positive in 78 H. pylori positive. Eight patients was ASCA positive in 50 H. pylori negative patients. ASCA in H. pylori positive was increasing more than that in H. pylori negative patients significantly. ASCA positivity was found to be correlated with eradication. All successful eradication patients were ASCA negative after treatment even if 3 patients were ASCA positive before eradication therapy. Our results show that ASCA is associated with both peptic ulcer and H. pylori infection.

DOP53 In-depth characterisation of the serum antibody epitope repertoire in Inflammatory Bowel Disease by high-throughput phage-displayed immunoprecipitation sequencing

Abstract Background Patients with IBD show distinct antibody responses, particularly against microbiota. However, a comprehensive overview of the antibody epitope repertoire in IBD is lacking. Here, we characterized serum antibody responses in patients with IBD and population controls using a high-throughput phage-displayed immunoprecipitation sequencing (PhIP-seq) workflow and associated these to disease phenotypes and the faecal microbiome. Methods PhIP-seq was leveraged to characterise antibody responses against 344,000 rationally selected peptide antigens in 497 patients with IBD which were compared with 1,326 individuals from a population-based cohort (Fig. 1A-B). Antibody profiles were linked to 23 IBD-specific clinical features such as disease location and surgical history and to faecal microbiota composition (Fig. 1C). Results Patients with IBD demonstrated distinct antibody epitope repertoires compared with individuals from the general population, with 373 differentially abundant antibody-bound peptides (202 overrepresented, 171 underrepresented) belonging to bacterial flagellins (69), virulence factors (102), other antigens of both commensal and pathogenic bacteria (90) as well as viruses (67) and food proteins (24) (Figure 2). In particular, antibody responses against bacterial flagellins, many of which belong to Lachnospiraceae bacteria (e.g. Roseburia spp.), but also Eubacterium spp. and pathogens (e.g. Legionella, Clostridium, Burkholderia) dominated in patients with Crohn’s disease (CD), and were associated with ileal disease involvement and more complicated disease behaviour (e.g. fibrostenotic disease, surgical history) as well as anti-Saccharomyces cerevisiae antibody positivity. Furthermore, many other antigens were newly identified, e.g. decreased responses to E. coli virulence factors and genome polyproteins of enteroviruses, and increased responses to food antigens (wheat, barley) and autoantigens (particularly collagen type I and VI). Antibody epitope repertoires were able to accurately discriminate CD from population controls (area under the curve [AUC]=0.88, test set evaluation), showing very high discriminative performance (positive and negative predictive value of 72% and 93%, respectively, representing predicted classes in test set) (Fig. 3A-C), which was less accurate for ulcerative colitis (UC) (Fig. 3D-F). Conclusion This study demonstrates the size, diversity and complexity of systemic antibody epitope repertoires in patients with IBD compared to controls, showing that distinct clinical phenotypes of IBD are characterized by unique antibody signatures. PhIP-seq is a powerful tool for identifying systemic immune-based biomarkers and exposing novel immunological targets in immune-mediated inflammatory diseases like IBD.

Meta-analysis of anti-Saccharomyces cerevisiae antibodies as diagnostic markers of Behçet’s disease with gastrointestinal involvement

ObjectiveDue to common exposure to yeast in the alcoholic and baking industry, positive rate of anti-Saccharomyces cerevisiae antibodies (ASCA) is reportedly high in patients with Behçet’s disease (BD) who have...

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa

Anti-Saccharomyces cerevisiae IgG and IgA antibodies are associated with systemic inflammation and advanced disease in hidradenitis suppurativa

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.

ASCA (Anti-Saccharomyces cerevisiae Antibody) in Patients With Scleroderma.

The majority of scleroderma (SSc) patients present gastrointestinal involvement. Motility is usually compromised but few studies address permeability changes in the intestinal wall. ASCA (anti-Saccharomyces cerevisiae antibodies) positivity is associated with increased intestinal permeability. In this study we aimed to investigate ASCA positivity in SSc patients and its association with clinical, serological and epidemiological data. Seventy-four SSc patients and 57 healthy controls were studied for ASCA (IgG and IgA) positivity by ELISA. ASCA positivity was associated with demographic, clinical severity index (by Medsger score) and serological data in SSc patients. ASCA-IgG was positive in 32/74 (43.2%) patients of the SSc group and 1/57 (1.7%) of controls (p < 0.0001); ASCA-IgA was positive in 12/74 (16.2%) of the SSc group and 3/57 (5.2%) of controls (p = 0.05). In univariate analysis, ASCA-IgG presence was associated positively with African ethnic background (p < 0.001) and negatively associated with anticentromere antibodies (p = 0.013); ASCA-IgA had a negative association with Medsger score (p = 0.05). In multivariate analysis ASCA-IgG associated independently only with African ethnic background. Positivity for ASCA-IgG and ASCA-IgA is higher among scleroderma patients than controls. African descendants have more positivity for ASCA-IgG. ASCA-IgA is less frequent in patients with a more severe disease.

The Long-Term Predictive Properties of the Paris Classification in Paediatric Inflammatory Bowel Disease Patients.

The Paris modification of the Montreal classification for children with inflammatory bowel disease was accepted in 2011. We aimed to investigate the long-term clinical outcomes of patients diagnosed with IBD during childhood in a population-based cohort according to the Paris classification at diagnosis. The medical records of paediatric inflammatory bowel disease patients, diagnosed from 2000 to 2016, were reviewed retrospectively. Main outcome measures included time to first flare, hospitalisation, surgery, and biologic therapy. In Crohn's disease patients [n = 301, median age 14.2 years], colonic location was associated with higher prevalence of extraintestinal manifestations, whereas ileal location and complicated behaviour were associated with anti-Saccharomyces cerevisiae antibody positivity. During a median follow-up of 9.1 years (interquartile range [IQR]of 4.7-12.3), complicated behaviour at diagnosis was associated with increased risk for surgery (hazard ratio[ HR] = 2.7, p < 0.001] and hospitalisation [HR = 1.5, p = 0.01] but not with the risk for flare or stepping-up to biologic therapy. Isolated colonic disease was associated with a decreased risk of surgery [HR = 0.25, p = 0.02]. During a median follow-up of 8.5 years [interquartile range of 5.1-12], in patients with ulcerative colitis [n = 126, median age 13.7 years], severe disease at diagnosis but not disease extent was associated with the risk for colectomy [HR = 3.5, p = 0.002], hospitalisation [HR = 3.3, p < 0.001], flare [HR = 2.4, p < 0.001] and biologic therapy [HR = 2.6, p = 0.001]. The Paris classification for paediatric inflammatory bowel disease has clear predictive properties. Complicated disease and ileal location at diagnosis in Crohn's disease, and severity of disease but not its extension in ulcerative colitis, predict long-term worse outcomes.

Clinical utility of serodiagnostic testing in pediatric inflammatory bowel disease

Background: Among children and adolescents, the diagnosis of inflammatory bowel disease (IBD) is often missed or delayed because of the nonspecific nature of the clinical symptoms. In such instances noninvasive and accurate diagnostic tests that would accurately distinguish IBD from functional disorders would be most valuable to clinicians. Several serological markers have been used as non-invasive diagnostic tools in IBD pediatric patients. The aim of our study was to determine the prevalence and diagnostic accuracy of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), anti-exocrine pancreatic antibodies (PAB) and anti-goblet cells antibodies (GAB) alone and in combination in children and adolescents with IBD. Patients and methods: Serum specimens were analyzed for p-ANCA, ASCA IgG, ASCA IgA, PAB and GAB antibodies in 49 children and adolescents with confirmed IBD and 53 non-IBD controls. P-ANCA, PAB and GAB antibodies were determined by indirect immunofluorescent test and ASCA by enzyme-linked immunosorbent assay. All patients with Crohn’s disease (CD) had genotyping performed using a sequence specific PCR directed against the wild type and the three principal mutations of NOD2/CARD15 gene. Disease location, body mass index (BMI) and disease activity by pediatric Crohn’s disease activity index (PCDAI) at the time of diagnosis were determined in CD patients. Results: The prevalence of p-ANCA in patients with UC and ASCA in CD patients was high (82.3 % and 67.9 %, respectively). Positivity for PAB antibodies in CD and GAB in UC was lower (35.7 % and 23.5 %, respectively). Accuracy data (sensitivity, specificity, PPV, NPV, respectively) for differentiating IBD from non-IBD controls were as follows: p-ANCA: 82 %, 100 %, 100 %, 94 %; ASCA IgG: 68 %, 94 %, 86 %, 84 %; ASCA IgA: 54 %, 100 %, 100 %, 80 %; PAB: 36 %, 98 %, 91 %, 74 %; GAB: 23 %, 100 %, 100 %, 80 %. In distinguishing CD from UC we found out the following accuracy data (sensitivity, specificity, PPV, NPV, respectively): p-ANCA: 82 %, 82 %, 74 %, 88 %; ASCA IgG: 68 %, 100 %, 100 %, 65 %; ASCA IgA: 54 %, 100 %, 100 %, 57 %; PAB: 36 %, 100 %, 100 %, 49 %; GAB: 23 %, 100 %, 100 %, 68 %. There were no significant association between ASCA positivity and the three major mutations of NOD2/CARD15 gene, disesase location and family history in CD patients, however an association between BMI and disease activity at the time of diagnosis was found out. Conclusions: Specificity and positive predictive value of serological markers p-ANCA, ASCA IgG, ASCA IgA, PAB and GAB for IBD alone and in combination are high and which make them useful in diagnosis of inflammatory bowel disease in day-to-day clinical practice, particulary in making decision about performing invasive diagnostic procedures. Because of low sensitivity they are less useful as screening tests for inflammatory bowel disease in pediatric population.

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.

Midkine in vitamin D deficiency and its association with anti-Saccharomyces cerevisiae antibodies.

The growth factor midkine (MK) is a protein that is involved in cancer, inflammation, immunity. Vitamin D is a potent immunomodulator. Anti-Saccharomyces cerevisiae antibody (ASCA) is reported in autoimmune disorders, some of which are among the causes of vitamin D deficiency. The objective of this study was to investigate a possible association of MK and ASCA with vitamin D deficiency. 208 adults presented to internal medicine outpatient clinic for history and physical examination has been studied. Serum biochemistry, vitamin D, MK, ASCA-IgG and -IgA, IL-1β, IL-6, IL-8, TNF-α, PDGF, VEGF were obtained. Vitamin D deficiency was 74.2%. Serum MK level was significantly higher in vitamin D-deficient compared to vitamin D-sufficient individuals (1138.1 ± 262.8 vs 958.6 ± 189 pg/mL, respectively; P < 0.009). Serum MK levels were also significantly higher in both ASCA-IgG and -IgA positives compared to negatives (1318.5 ± 160.3 vs 1065.5 ± 256.1, P = 0.008 and 1347.7 ± 229.7 vs 1070.1 ± 250.9 pg/mL, P = 0.011, respectively). Vitamin D was significantly lower in ASCA positives (P = 0.044).Vitamin D showed positive correlation with IL-1β (r 0.338, P < 0.009) and negative correlation with VEGF (r -0.366, P < 0.004). MK was significantly elevated in vitamin D deficiency and associated with ASCA positivity which was significantly increased in vitamin D deficiency. These findings suggested that molecular mechanism of vitamin D deficiency may be related with some inflammatory processes.

Intestinal Behçetʼs Disease Does Not Follow the Silk Road

Introduction: Behçet's disease (BD) is a chronic multi-system inflammatory disease with an unknown etiology and carries a high morbidity. It is most prevalent in Eastern Asia and along the Mediterranean basin, an area referred to as “The Silk Road.” The diagnosis of BD is largely based on the International Study Group (ISG) criteria which are more specific than sensitive. ISG criteria do not include intestinal manifestations, a feature more commonly seen in the West. Pathophysiology of BD is attributed to an environmental trigger in a genetically susceptible host, and likely explains the different manifestations seen here in the West. Intestinal BD is one of several findings that are not typically seen along “The Silk Road”. Herein we report a rare case of Intestinal BD and compare Western and Traditional BD. Case Report: A 25-year-old male with a history of painful oral apthous ulcers, pericarditis and diffuse papulopustular rash presented to the ED with two terminal ileal perforations (Figure 1). Pathology demonstrated mucosal necrosis with active inflammation and no chronic inflammatory changes. Post-surgical laboratory studies showed an elevated CRP of 35.57 mg/dL, ESR of 82mm/h, and a positive anti-Saccharomyces cerevisiae antibody. Rhematological workup including: ANA, RF, PR3 antibody, MPO antibody, ANCA, SSA, SSB, Smith antibody, SCL-70 and anti-Jo-1 antibodies were all negative. Pathergy test was negative. His pericarditis symptoms improved with colchicine and prednisone prior to discharge.Figure 1Discussion: Our patient did not meet the current ISG criteria for traditional BD, however, he clearly showed findings typically seen in western patients with BD which include intestinal manifestions, cardiac involvment and lack of pathergy reaction and ocular changes. Our investigation demonstrates that the clinical manifestations common to this disorder vary among geographic and ethnic populations (Table 1). Commonly used criteria for the diagnosis of BD may not be sensitive for some populations such as Western BD, potentially leading to underdiagnoses and mismanagement. Recognition and select inclusion of these differences may be one way to assist with diagnosing Western BD in the future. As our knowledge of BD continues to evolve, so must the population-specific criteria used to define BD.Table 1: Prevelance of Clincial Features in Western and Traditional Behçet's Disaease

An investigation into the relationship between anti-Helicobacter pylori and anti-Saccharomyces cerevisiae antibodies in patients with axial spondyloarthritis and Crohn disease.

Spondyloarthritis (SpA) is a musculoskeletal inflammatory disease linked with immune responses to intestinal microbiota, and subclinical intestinal ulcerations that are closely related to inflammatory bowel diseases. Helicobacter pylori is a common cause of gastroduodenal ulceration, and anti-Saccharomyces cerevisiae antibodies (ASCA) are associated with intestinal inflammation in both Crohn disease (CD) and SpA. We investigated the relationship between H. pylori and ASCA. Ninety-one patients with axial SpA and forty with CD were included. ASCA IgG/IgA and anti-H. pylori IgG titers were assessed by ELISA. The proportion of ASCA+ patients in the positive and negative anti-H. pylori IgG groups with SpA and CD were compared using Chi-square tests, and correlations were evaluated using the Spearman's coefficient. Anti-H. pylori IgG titers were significantly negatively correlated with the ASCA IgG (r = -0.563, p < 0.001) and IgA (r = -0.342, p = 0.019) titers in the axial SpA patients. The same pattern of negative correlation was also observed in the CD patients. Anti-H. pylori+ serology was significantly more frequent in axial SpA patients than in those with CD (52.4 vs. 18.4 %, p < 0.001), while ASCA+ serology was significantly more frequent in CD patients than in SpA patients. A negative correlation between the anti-H. pylori titers and ASCA was found for axial SpA and CD. Anti-H. pylori+ serology was more frequent in SpA than in CD, while ASCA positivity was more frequent in CD patients than in those with SpA. A possible influence of H. pylori on the development of ASCA needs further investigation.

Characteristics of Inflammatory Bowel Disease Serology in Patients With Indeterminate Colitis

Inflammatory bowel disease (IBD) serology testing is often used in patients with indeterminate colitis (IC) to help distinguish between ulcerative colitis (UC) and Crohn's disease (CD). We investigated the performance of serology testing in predicting future diagnosis in this setting. This was an observational study of individuals with IC at a single center who underwent IBD serology testing [anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), and anti-outer membrane porin C antibody (anti-OmpC)] and had at least 12 months follow-up from the time of serology test results. A total of 117 individuals with IC and with 1-year follow-up data were enrolled. All IC patients had endoscopic and histologic evidence of colitis at enrollment. One year after serology testing, 58 (50%) individuals with IC were diagnosed with UC, 49 (42%) with CD, and 10 (9%) remained labeled with IC. The sensitivity/specificity of an initial positive pANCA for a subsequent diagnosis of UC was 78%/44%. For ASCA and anti-OmpC, the results were 18%/84% and 27%/75%, respectively, for a subsequent diagnosis of CD. A positive pANCA test was associated with a likelihood ratio (LR) of 1.4 [95% confidence interval (CI), 1.1-1.8] for a subsequent diagnosis of UC at 1 year. Neither positive ASCA (LR 1.1; 95% CI, 0.5-2.5) nor anti-OmpC (LR 1.1; 95% CI, 0.6-2.0) was associated with a subsequent diagnosis of CD in patients with IC. The disease phenotype in the majority of individuals initially labeled with IC evolved to be more consistent with either UC or CD on follow-up. pANCA, ASCA, and anti-OmpC, individually, were of limited utility in predicting a patient's subsequent disease phenotype.

Mannose-binding lectin deficiency is not associated with Anti-Saccharomyces cerevisiae antibody in Korean Crohn's disease patients

BackgroundMannose-binding lectin (MBL) is a pattern-recognition molecule and an important component of the innate defense system. Anti-Saccharomyces cerevisiae antibody (ASCA) is a well known serologic marker of Crohn's disease (CD). This study aimed to investigate the association between MBL, ASCA, and clinical features in Korean CD patients. MethodTwo hundred and eighty-three well-characterized CD patients were included. MBL concentrations, serum IgG and IgA concentrations of ASCA were determined by ELISA. Low MBL concentrations were defined as serum MBL concentrations <500ng/ml. ResultLow MBL concentrations were observed in 41 CD patients (14.5%). No differences in MBL concentrations were detected according to the age at diagnosis, behavior, or the location of patients with CD. MBL concentrations and the frequency of low MBL concentrations did not differ according to ASCA positivity. The presence of perianal involvement (p=0.043), younger age at diagnosis (p=0.021), and intestinal surgery (p=0.047) were more frequently associated with ASCA positive patients. ConclusionMBL concentration is not associated with clinical features of CD patients or ASCA positivity. ASCA positivity is associated with a severe clinical course in Korean CD patients.

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....

Clinical significance and prevalence of anti-Saccharomyces cerevisiae antibody in Chinese patients with primary biliary cirrhosis

Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) and its prevalence in Chinese primary biliary cirrhosis (PBC) patients have not been characterized and therefore needs to be defined. Enzyme-linked immunosorbent assay was used to test ASCA in sera from 198 PBC patients, 85 patients with other liver diseases (OLD) and 35 health controls (HC). Indirect immunofluorescence was used to detect anti-mitochondrial antibodies (AMA) in PBC. Results showed that the frequency of ASCA in PBC, 29.8%, was higher than other disease groups. And ASCA occurred more frequently in PBC patients with positive anti-gp210 than the negative ones. Also, ASCA was detected in 7 out of 15 PBC negative for AMA. Some liver-related biochemical indices and inflammatory indices were significantly higher in PBC patients with positive ASCA (p<0.05). In conclusion, the prevalence of ASCA in Chinese PBC patients is 29.8%. PBC patients with positive ASCA are associated with more severe liver injury, and ASCA-IgA might be related to disease activity of PBC.