anti-Saccharomyces Cerevisiae Research Articles

Anti-Saccharomyces cerevisiae (ASCA) in patients with severe obesity undergoing bariatric surgery: 12-month follow-up.

Severe obesity is linked to a low-grade inflammatory process due to enlarged adipose tissue, resulting in elevated pro-inflammatory cytokines. Bariatric surgery induces anatomical changes, causing intestinal inflammation marked by anti-Saccharomyces cerevisiae (ASCA) antibodies. This study aimed to assess ASCA IgG/IgA levels preoperatively and 12 months post-surgery, correlating them with systemic inflammation markers (IL-6, CRP, MCP-1). Participants (BMI > 35 kg/m2) were recruited in South Brazil. Severe obesity individuals showed elevated IL-6 (p=0.002), CRP (p<0.0001), and MCP-1 (p<0.0001) compared to lean controls. ASCA IgA was significantly higher in severe obesity (p=0.0019). Post-surgery, ASCA IgG/IgA significantly decreased (p=0.0046 and p<0.0001), along with IL-6, MCP-1, and CRP, confirming weight loss and reduced inflammation. Hypertrophic adipose tissue, producing pro-inflammatory cytokines, associates with increased intestinal inflammation. Bariatric surgery-induced anatomical changes contribute to long-term weight loss and reduced systemic and intestinal inflammation.

Coincidence of antibodies against Hwp1 and ASCA, two distinct molecular targets of Candida albicans, reinforces the link between this fungal species and coeliac disease

ABSTRACT Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibodies (ASCA), a serological marker of Crohn’s disease. ASCA has also been reported in other autoimmune diseases, including coeliac disease (CeD). A strong antibody response against Hwp1, a protein associated with invasive hyphal form of C. albicans which presents peptide sequence homologies with gliadin, has also been described in CeD. This observation supports the hypothesis that C. albicans hyphal transition in C. albicans may trigger CeD onset through a mechanism of molecular/antigenic mimicry. In this study, we assessed whether the anti-C. albicans oligomannose and anti-Hwp1 protein responses may be linked despite their different pathophysiological significance. The measurement of ASCA levels in a cohort of patients involved in our previous Hwp1 study showed a significant correlation between the two biomarkers. This new observation further reinforces the link between C. albicans and CeD.

Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease

Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. Most EIMs occurred more commonly in female subjects (overall EIM: P= 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P= 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P= 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P= 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P= 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P= 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P= 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P= 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.

Features of diagnostic search in Churg–Strauss syndrome. Case report

Churg–Strauss syndrome is a rare systemic vasculitis affecting small-caliber vessels, which has characteristic clinical manifestations in the forms of allergic rhinosinusitis, bronchial asthma (BA), eosinophilia, and pulmonary infiltrates. The reason for late diagnostics is gradual manifestation of symptoms, that typical of systemic diseases. Improving the knowledge of pediatricians, pulmonologists about the role of diagnostic search in Churg–Strauss syndrome for further routing, monitoring and correction of patient therapy. A 17-year-old boy with BA was admitted to the pulmonology department for clarification, verification of the diagnosis, and selection of therapy. Instrumental and laboratory examination was carried out: on the computer tomography (CT) scan of the thoracic organs "migrating" infiltration of both lungs, based on laboratory data may correspond to eosinophilic zones. On the CT scan of the nasal sinuses polysinusitis, polyposis; external respiration function (spirography) – no pathology; myeloperoxidase-antineutrophil cytoplasmic antibodies (ANCA) – 14 U/ml (normal 5), anti-proteinase 3 anti-neutrophil ANCA – 30 U/ml (normal 5), anti-Saccharomyces cerevisiae antibodies – 6.3–7.2 U/ml, eosinophilia (12%, abs 840 c). The result of the level of antibodies was negative later. Churg–Strauss syndrome was based on the American College of Rheumatology criteria: BA, eosinophilia 10% (abs 840), rhinosinusitis, migrating infiltrations on CT scan. He was discharged for asthma combination therapy with high age doses of inhaled corticosteroids. After treatment his condition improved, there was no need for systemic corticosteroids. The described clinical case clearly demonstrates the difficulty and duration of diagnosing Churg–Strauss syndrome due to the stage-by-stage course of the disease, the frequent (33% of cases) absence of laboratory evidence of vasculitis (ANCA-neg.) significant difficulty of verifying the diagnosis at early stages. The diagnosis provides for a comprehensive and interdisciplinary approach to diagnosis and treatment.

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

ObjectiveThis study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). MethodsPediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. ResultsIn all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. ConclusionSerological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.

Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder.

Fungal plasma biomarkers have not been studied in patients with unhealthy alcohol use and no apparent end-stage liver disease. We examined the prevalence of fungal plasma biomarkers, assessed by the presence of anti-Saccharomyces cerevisiae antibodies (ASCA; IgA and IgM), and its disease correlates in patients with alcohol use disorder (AUD). We performed logistic regression analyses to detect the association between clinical and laboratory characteristics and the presence of fungal plasma biomarkers. We included 395 patients (75.9% male, median age of 49 years, and median body mass index of 25.6) who drank a median of 150 g of alcohol daily and had a median duration of AUD of 20 years. ASCA IgA and IgG were present in 34.4% and 14.9%, respectively, and 9.9% had both ASCA IgA and ASCA IgG. The presence of ASCA IgA was associated with male sex (p < 0.01); values of serum aspartate transferase (AST) (p = 0.02), gamma-glutamyl transferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01), and bilirubin in the highest quartile (p < 0.01); Fibrosis-4 Index (FIB-4) values suggestive of advanced liver fibrosis (p < 0.01); and values of the macrophage activation factors sCD163 (p < 0.01) and sCD14 (p < 0.01), the cytokine IL-6 (p = 0.01), and lipopolysaccharide-binding protein in the highest quartile (p < 0.01). The presence of ASCA IgG was associated with omeprazole use (p = 0.04); values of AST (p = 0.04) and GGT (p = 0.04) in the highest quartile; FIB-4 values suggestive of advanced liver fibrosis (p < 0.01); and values of sCD163 (p < 0.01) in the highest quartile. The variables associated with the presence of both ASCA IgA and IgG were male sex (p = 0.04) and values of GGT (p = 0.04) and sCD163 in the highest quartile (p < 0.01). In AUD patients, the presence of fungal biomarkers in plasma was common and associated with FIB-4 values suggestive of advanced liver fibrosis and with markers of liver damage, monocyte activation, and microbial translocation, male gender, and omeprazole use. These findings suggest that the presence of plasma anti-Saccharomyces cerevisiae antibodies could be used as a biomarker for an elevated risk of progressive liver disease in patients with AUD.

WED-291 - Anti-Saccharomyces cerevisiae antibodies predict severe liver disease and advanced fibrosis in patients with primary sclerosing cholangitis and inflammatory bowel disease

WED-291 - Anti-Saccharomyces cerevisiae antibodies predict severe liver disease and advanced fibrosis in patients with primary sclerosing cholangitis and inflammatory bowel disease

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.

Chronic Inflammatory Intestinal Disorders in Hidradenitis Suppurativa

Background: Intestinal symptoms are common in patients with hidradenitis suppurativa (HS). HS patients may experience a broad spectrum of chronic inflammatory intestinal disorders (CIID), not exclusive to inflammatory bowel diseases, which are diagnosed by colonoscopy and intestinal biopsies. The frequency of CIID in patients with HS has not been investigated. Objective: The objectives of this study were to determine the occurrence of CIID in HS and characterize this clinical population. Furthermore, the feasibility of using faecal calprotectin (FC) test or anti-Saccharomyces cerevisiae antibody (ASCA) levels to assess the colonic inflammation of CIID in HS patients was investigated. Methods: All newly diagnosed and untreated HS patients (n = 74) were referred to a gastroenterologist for FC followed by colonoscopy after informed consent. C-reactive protein (CRP), white blood cell count, nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) polymorphism, and ASCA levels were measured. Patients were divided into HS-only and HS with CIID (HS + CIID) groups, based on the absence or presence of CIID. Laboratory and clinical parameters (age, gender, HS onset, clinical stage, family history, body mass index (BMI), smoking) were compared between the groups. Results: Thirteen patients complained gastrointestinal symptoms prior to any examination, including 11 in the HS + CIID group. The CIID frequency in HS was 28.4% (n = 21/74), based on colonoscopy and histology. Significantly more patients had severe disease state in the HS + CIID group compared with the HS-only group, and BMI was significantly lower in the HS + CIID group (28.20 ± 5.58 vs. 32.74 ± 6.45, p = 0.006). FC positivity occurred significantly more in HS + CIID patients compared with HS-only patients (90.48% vs. 3.77%, p < 0.001), and ASCA IgG levels were significantly elevated in HS + CIID patients (22.08 ± 23.07 vs. 8.41 ± 10.94 U/mL, p = 0.001). The FC test identified HS + CIID patients with 96.23% specificity and 91.3% sensitivity, while ASCA displayed 77.8% sensitivity and 76.3% specificity. Blood count, CRP, and the presence of NOD2 polymorphisms were indifferent between the two groups. Conclusion: A high frequency of CIID was detected in the examined HS population. The noninvasive FC test has high sensitivity and specificity for diagnosing CIID in HS patients. Concomitant CIID and HS may indicate the need for an early-start for biological treatment.

Anti-Saccharomyces cerevisiae Antibodies (ASCA) Researched by Tube Precipitins are Elevated in Patients with Dermatologic and Gastrointestinal Non-Ige-Mediated Hypersensitivity

Background: The presence of anti-Saccharomyces cerevisiae antibodies (ASCA) has been reported in the serum of patients with several immune-inflammatory diseases. Objective: To evaluate the presence of ASCA in patients with non-IgE-mediated hypersensitivity. Methods: A group of 222 patients with non-IgE-mediated hypersensitivity was divided into three groups according to dermatologic, gastrointestinal, and respiratory symptoms. Group D was composed of 163 patients with dermatologic symptoms diagnosed as intrinsic atopic dermatitis and/or non-IgE-mediated urticaria. Group G was composed of 23 patients diagnosed with non-IgE-mediated gastrointestinal food allergies. Group R was composed of 36 patients with respiratory symptoms diagnosed as non-IgE-mediated rhinitis and/or non-IgE-mediated asthma. Results: The Wilcoxon-Mann-Whitney U test comparing the precipitin’s titers of group G and group D showed a non-significant p-value of 0.83366. The Wilcoxon-Mann-Whitney U test comparing the precipitin’s titers of group R and group G showed a significant p-value of 0.00034. The Wilcoxon-Mann-Whitney U test comparing the precipitin’s titers of group R and group D showed a significant p-value &lt; 0.0001. Conclusion: The patients with respiratory symptoms diagnosed as non-IgE-mediated rhinitis and/or asthma presented significantly less humoral immunoreactivity against S. cerevisiae than patients with non-IgE-mediated food allergy and patients with intrinsic atopic dermatitis and/or non-IgE-mediated urticaria. The elevation of ASCA titers may be an unspecific marker of intestinal hyperpermeability, and possibly may participate in Gell and Coomb’s types II and/or type III hypersensitivity reactions responsible for the patient’s dermatologic and gastrointestinal symptoms.

Elevated serum anti-Saccharomyces cerevisiae antibody accompanied by gut mycobiota dysbiosis as a biomarker of diagnosis in patients with de novo Parkinson disease.

Intestinal inflammation and gut microbiota dysbiosis contribute to Parkinson disease (PD) pathogenesis, and growing evidence suggests associations between inflammatory bowel diseases (IBD) and PD. Considered as markers of chronic gastrointestinal inflammation, elevated serum anti-Saccharomyces cerevisiae antibody (ASCA) levels, against certain gut fungal components, are related to IBD, but their effect on PD is yet to be investigated. Serum ASCA IgG and IgA levels were measured using an enzyme-linked immunosorbent assay, and the gut mycobiota communities were investigated using ITS2 sequencing and analyzed using the Qiime pipeline. The study included 393 subjects (148 healthy controls [HCs], 140 with PD, and 105 with essential tremor [ET]). Both serum ASCA IgG and IgA levels were significantly higher in the PD group than in the ET and HC groups. Combining serum ASCA levels and the occurrence of constipation could discriminate patients with PD from controls (area under the curve [AUC]=0.81, 95% confidence interval [CI] = 0.76-0.86) and from patients with ET (AUC=0.85, 95% CI=0.79-0.89). Furthermore, the composition of the gut fungal community differed between the PD and HC groups. The relative abundances of Saccharomyces cerevisiae, Aspergillus, Candida solani, Aspergillus flavus, ASV601_Fungi, ASV866_Fungi, and ASV755_Fungi were significantly higher in the PD group, and enriched Malassezia restricta was found in the HC group. Our study identified elevated serum ASCA levels and enriched gut Saccharomyces cerevisiae in de novo PD.

P243 The association between serological markers ASCA and ANCA and response to induction treatment in therapy-naïve children with inflammatory bowel disease: an international prospective study

Abstract Background Pediatric-onset inflammatory bowel disease (PIBD) is a chronic disease with a heterogeneous spectrum. A better understanding of predicting factors for therapy response could improve personalized care and reduce complications. Possible predicting factors of a complicated disease behavior in PIBD are the presence of anti-Saccharomyces cerevisiae (ASCA) and antineutrophil cytoplasmic antibodies (ANCA) in the serum, though existing evidence is inconclusive. We aimed to investigate the association of serological markers ASCA and ANCA with short-term therapy response at 3 and 6 months in PIBD patients. Methods As part of the multicenter prospective observational PIBD-SETQuality study, blood from therapy-naïve PIBD patients (n=162) with a minimum follow-up of 6 months was analyzed for 3 serological markers (ASCA IgA, ASCA IgG and/or ANCA) at diagnosis. Outcome measures included clinical remission and biochemical remission (remission with CRP &amp;lt;0.5 mg/dl or fecal calprotectin &amp;lt; 300 mcg/g), small or moderate improvement after induction treatment, and therapy use at 3 and 6 months. To evaluate effect of ASCA titers, serology sum scores (SSS) were obtained by combining results of ANCA status and scores of ASCA titer quartiles, and compared between outcomes. Results ASCA IgA and IgG were more prevalent in Crohn’s disease (CD) patients [47% vs. 2% for IgA; 75% vs. 5% for IgG, p&amp;lt;0.001] and ANCA in ulcerative colitis/inflammatory bowel disease unclassified (UC/IBD-U) [43% vs. 11%, p&amp;lt;0.001] patients. ASCA IgA and IgG were not associated with markers of disease activity (albumin, CRP, wPCDAI) at diagnosis in children with CD, but ASCA IgG positivity was more prevalent in patients with an ileocolonic distribution (L3 57%, L2 6%, L1 37%, p=0.024). ANCA positivity was not associated with any disease characteristic at diagnosis. No association was found between clinical or biochemical remission status at 3 and 6 months and ASCA and ANCA positivity. Additionally, no association was found between ASCA and ANCA positivity and small or moderate response to induction therapy at 3 and 6 months. ASCA IgG positive patients had higher rates of anti-TNF use at 6 months compared to ASCA IgG negative patients [84% vs. 50%, p=0.041]. Patients with higher SSS did not tend to have poorer outcomes at 3 and 6 months compared to patients with lower SSS. Conclusion While serological markers ASCA and ANCA may provide a way to better differentiate between CD and UC/IBD-U in PIBD, this study did not find any association between ASCA and ANCA and short-term therapy response. ASCA IgG patients were more likely to have used anti-TNF at 6 months, possibly reflecting more severe disease.

DOP52 The faecal bacterial and fungal microbiome of newly-diagnosed, treatment naïve children with Crohn’s disease and the modifying effects of exclusive enteral nutrition and re-introduction of habitual diet

Abstract Background The fungal community (mycobiome) and immunological responses to specific fungi have been implicated in Crohn’s disease (CD) pathogenesis and its phenotype. There is limited data on profiling the mycobiome in paediatric CD and how it changes during treatment Methods Fungal (ITS2) and bacterial (16S rRNA) microbiome analysis in faecal samples (n=124) from n=34 CD children before, during (30 and 60 days) and after exclusive enteral nutrition (EEN) at food reintroduction (within 60 days of EEN completion), and from 31 healthy controls were profiled. IgA and IgG anti-Saccharomyces cerevisiae antibodies (ASCA) analysis by enzyme-linked immunosorbent assay, in blood, was also carried out for CD patients prior to EEN initiation. Results The global mycobiome composition (β diversity) was different between CD and healthy children (R2=0.050; p=0.007) and presented lower Chao1 richness (mean 24.3 vs 33.0; p=0.005) for the CD cases; 13 fungal operational taxonomic units (OTUs) differed between the two groups. Similar signals were observed for the bacterial microbiome but the difference in global community structure (β diversity) was more profound than the fungal community (R2=0.094; p&amp;lt;0.001). Treatment with EEN induced drastic changes in mycobiome composition (β diversity), which were more profound and more variable than the effects observed for the bacterial community. Of the OTUs with abundance significantly lower in CD than healthy controls prior to EEN, one, belonging to S. cerevisiae, significantly decreased during EEN (compared with baseline; p&amp;lt;0.001 and p=0.086 at 30 and 60 days on EEN). Patients whose faecal calprotectin was low (&amp;lt;250 mg/kg) during food reintroduction had a lower mycobiome richness than those whose FC was raised (&amp;gt;250 mg/kg). 29 fungal OTUs were significantly different between these two groups in samples taken during food reintroduction, following EEN. Patients who were ASCA positive had a higher abundance of three OTUs of S. cerevisiae. In co-occurrence network analysis, Simplicillium chinense, presented significant more interactions with members of the bacterial community, particularly OTUs which changed during EEN. After participants had returned to their regular diets these microbial effects reversed and community structure moved towards that observed prior to EEN. Conclusion The mycobiome of children with CD present features of dysbiosis similar to the bacterial microbiome and improvement in disease condition during EEN is strongly associated with changes in its composition.

Diagnostic value of different serological markers and correlation analysis with disease phenotype in inflammatory bowel disease

Objective: To explore the diagnostic value of different serological markers and the correlation with disease phenotype in inflammatory bowel disease (IBD). Methods: The clinical data of 445 IBD patients in Peking Union Medical College Hospital from June 2010 to December 2020 were retrospectively collected, including 223 cases of ulcerative colitis (UC) [111 males, 112 females, with a median age of 46(20,79) years] and 222 cases of Crohn's disease (CD) [147 males, 75 females, with a median age of 39 (19, 72) years]. The positive rates of serum anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), goblet cell autoantibodies (GAB) and pancreatic autoantibodies (PAB) in the two groups were analyzed. The sensitivity, specificity, positive predictive value and negative predictive value of UC and CD were calculated. Logistic regression was performed to analyze the relationship between different combinations of antibodies and disease phenotype. Results: The positive rates of ASCA and PAB in CD patients were 34.7% (77/222) and 38.3% (85/222), respectively, which were higher than those in UC patients [10.3% (23/223) and 4.5% (10/223), P<0.001]. The positive rate of ANCA in UC patients was 50.2% (112/223), which was higher than that in CD patients [5.4% (12/222), P<0.001]. The positive rates of serum GAB in CD and UC patients were 21.6% (48/222) and 28.3% (63/223), respectively, with no significant difference (P=0.760). In patients with CD, the sensitivity of mono-marker ASCA (+), dual-marker ASCA (+) ANCA (-), quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) in diagnosing CD was 34.7%, 32.9%, 20.7%, the specificity was 89.7%, 95.5%, 100.0%, the positive predictive value was 77.0%, 90.1%, 100.0%, and the negative predictive value was 58.0%, 58.7%, 55.9%, respectively. In patients with UC, the sensitivity of mono-marker ANCA (+), dual-marker ANCA (+) ASCA (-), quadruple-marker ANCA (+) ASCA (-) PAB (-) GAB (+) in diagnosing UC was 50.2%, 40.4%, 24.2%, the specificity was 94.6%, 95.5%, 100.0%, the positive predictive value was 90.3%, 90.0%, 100.0%, and the negative predictive value was 65.4%, 61.4%, 56.8%, respectively. Mono-marker ASCA (+) (OR=3.39, 95%CI: 1.59-7.21), dual-marker ASCA (+) ANCA (-) (OR=2.87, 95%CI: 1.34-6.14), triple-marker ASCA (+) ANCA (-) GAB (-) (OR=3.09, 95%CI: 1.31-7.31) and quadruple-marker ASCA (+) ANCA (-) PAB (+) GAB (-) (OR=3.15, 95%CI: 1.56-8.03) were associated with stenosis and/or penetrating type CD. The mono-marker ANCA (+) (OR=2.69, 95%CI: 1.42-5.12) and dual-marker ANCA (+) ASCA (-) (OR=2.11, 95%CI: 1.03-4.16) were associated with extensive colonic lesions in UC. Conclusion: Based on ASCA or ANCA, the combination with PAB or GAB, is conducive to IBD diagnosis, and is associated with stenosis and/or penetrating type of CD and extensive type of UC.

Newly Diagnosed Crohn's Disease Patients in India and Israel Display Distinct Presentations and Serological Markers: Insights from Prospective Cohorts.

Background: Crohn’s disease (CD) incidence is rising in India. However, features of newly diagnosed patients with CD in this population are largely unknown. The Indo-Israeli IBD GastroEnterology paRtnership (TiiiGER) aimed to investigate differences in presentation among patients with newly diagnosed CD in India and Israel, and to explore phenotype−serotype correlations. Methods: A prospective observational cohort study of consecutive adults (>18 years) conducted in two large referral centers in India and Israel (2014−2018). Clinical data, an antiglycan serological panel, and 20 CD-associated genetic variants were analyzed. Outcomes: complicated phenotype at diagnosis and early complicated course (hospitalizations/surgeries) within 2 years of diagnosis. Results: We included 260 patients (104, Indian (65.4%, male; age, 37.8); 156 Israeli (49.4%, male; 31.8, age)). Median lag time from symptoms onset to diagnosis was 10.5 (IQR 3−38) vs. 3 (IQR 1−8) months in Indian vs. Israeli patients (p < 0.001). Complicated phenotype at diagnosis was observed in 48% of Indian and 30% of Israeli patients (p = 0.003). Complicated phenotype was associated with higher anti-Saccharomyces cerevisiae antibody (ASCA) seropositivity rate among Israeli patients (p < 0.001), but not among Indian patients. Antiglycan serology did not correlate with the tested genetic variants. Early complicated course occurred in 28 (18%) Israeli and 13 (12.5%) Indian patients. The time from diagnosis to complication was comparable (log rank p = 0.152). Antiglycan serology did not correlate with a complicated early course in either cohort. Conclusions: There are significant differences in patients presenting with newly diagnosed CD in India and Israel, including phenotype and distinct biomarkers at diagnosis. These differences suggest different genetic and environmental disease modifiers.

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.

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

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

S2733 How to Manage Silent Inflammatory Bowel Disease

Introduction: The incidence and prevalence of inflammatory bowel diseases (IBD), Ulcerative Colitis (UC) and Crohn’s Disease (CD), are increasing worldwide. The pathogenesis of IBD is multifactorial and the disease has a pre-clinical stage where inflammation and damage progress to develop intestinal symptoms. However, some patients in the pre-clinical stage of IBD may be identified on screening modalities. This finding often poses a dilemma as asymptomatic patients may not be willing to initiate medical treatment. Here we describe two cases of pre-clinical IBD found on screening colonoscopy. Case Description/Methods: Patient 1 is an asymptomatic 47-year-old female without significant past medical history who presented for screening colonoscopy. Colonoscopy revealed ileocecal valve stenosis with inflammation that prevented intubation beyond the valve but tissue sample of the ileum was obtained (Figure A-B). Biopsies revealed focal active ileitis with mild glandular distortion and rare pseudopyloric glandular distortion. Magnetic resonance elastography (MRE) showed findings of the terminal ileum with marked bowel wall thickening, luminal narrowing, upstream dilatation suggestive of stricture and penetrating disease with enteroenteric and enterocolonic fistulas. Patient was classified A3/L3/B3. Patient 2 is an asymptomatic 51-year-old female with a past medical history of gastroesophageal reflux disease and anxiety who presented for screening colonoscopy. Colonoscopy was noted to have a patchy, erythematous and ulcerated ileum, and distorted IC valve (Figure C-D). Biopsies revealed severe active ileitis with ulceration. Patient subsequently underwent further workup revealing positive anti-Saccharomyces cerevisiae antibodies (ASCA). Patient was classified as A3/L1/B1. Discussion: Identifying pre-clinical IBD on screening modalities should not dissuade a clinician from appropriately managing moderate to severe cases of IBD. It may be difficult to decide who to treat because such patients are asymptomatic, but persistent inflammation has been shown to be associated with higher rates of hospitalization, surgery, or new abscesses or fistulas. Clinicians can follow up with lower risk patients to monitor symptoms like patient 2, but asymptomatic fistulizing disease and stenoses are high risk like seen in patient 1. Awareness of pre-clinical IBD is important and further discussions about screening and management are warranted.Figure 1.: Screening Colonoscopy of Patients A – Patient 1 Ileocecal valve B – Patient 1 Stenosed Ileocecal valve unable to be traversed C – Patient 2 Normal appearing ileocecal valve D – Patient 2 Terminal ileum ulcer.

Dyspepsia-Like Symptoms in Helicobacter pylori-Negative Chronic Gastritis are Associated with ASCA-, ANCA-, and Celiac Seropositivity but Not with Other Autoimmune Parameters: A Single-Centre, Retrospective Cross-Sectional Study.

IntroductionDyspeptic symptoms are frequent in the general population, with a high socioeconomic burden. Helicobacter pylori (H. pylori) might be a possible etiological factor; however, it is also common in H. pylori negative gastritis. Clarification of the underlying aetiology might be beneficial to set up the optimal treatment strategy for dyspepsia and chronic gastritis (CG) itself. We aimed to assess the prevalence of dyspeptic symptoms in patients with H. pylori negative CG and explore autoimmunity’s possible role.MethodsThis retrospective study included data from patients with H. pylori negative CG. Exclusion criteria were (1) acute gastritis; (2) reactive gastropathy; (3) subjects without any serology testing results; (4) H. pylori positivity; (5) presence of atrophy, intestinal metaplasia (IM), gastroesophageal reflux disease (GERD), ulcer, or cancer. The following endpoints were assessed (1) the rate of dyspepsia-like symptoms; (2) association between dyspepsia and autoimmune disease-related seromarker positivity (AISP); (3) frequency of other symptoms in CG and its association with AISP; (4) location of the inflammation and its association with AISP.ResultsFrom a total of 285 patients, 175 were included in this study. Among these patients, 95 experienced dyspeptic symptoms (54.29%) and were associated more with AISP (p = 0.012), especially with celiac seropositivity (p = 0.045), anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) positivity (p = 0.043). A significant association was not found with other tested autoimmune (AI)-related antibody positivity.ConclusionPositivity of seromarkers of autoimmune diseases in chronic gastritis may predispose to have dyspeptic symptoms and may be the causative factor behind some cases of uninvestigated dyspepsia. These data suggest that further prospective studies are needed to clarify whether screening for autoantibodies in patients with dyspepsia is cost-effective and helps the earlier diagnosis of autoimmune diseases.

Anti-Saccharomyces cerevisiae Antibodies Are Only Modestly More Common in Subjects Later Developing Crohn's Disease

BackgroundThe pathogenic processes in the preclinical phase of inflammatory bowel disease (IBD) are mainly unknown.AimsTo study typical antibodies for IBD in the preclinical phase in a cohort of Northern Sweden.MethodsAntibodies typical for IBD (ASCA, pANCA, lactoferrin-ANCA, antibodies to goblet cells, and pancreas antigen) were analyzed in 123 subjects with preclinical ulcerative colitis (UC), 54 subjects with preclinical Crohn's disease (CD) and in 390 sex- and age-matched controls. In addition, in a subset of subjects, inflammatory markers (CRP, albumin, calprotectin and ferritin) were measured in plasma.ResultsThe mean years between blood samples and IBD diagnosis were for UC 5.1 (SD 3.5) years and CD 5.6 (SD 3.5) years. There was no difference in the proportion of overall positive antibodies between subjects who later developed IBD compared to controls (16.9% vs. 12.3%; p = 0.137). The subjects who later developed CD had a significantly higher proportion of positive ASCA compared to controls (9.3% vs 2.8%; p = 0.034), but for all other antibodies, there were no differences compared to control subjects. Subjects with preclinical IBD and elevated antibodies showed significantly higher plasma calprotectin levels compared to subjects without antibodies (980 μg/L vs 756 μg/L; p = 0.042), but there was no difference in the levels of CRP, albumin and ferritin.ConclusionsWe found no significant increase in antibodies typical for IBD years before diagnosis except for ASCA, which was slightly more common in subjects who later developed CD. Very few subjects had detectable antibodies to goblet cells and pancreas antigen.