anti-Saccharomyces Cerevisiae Antibodies Research Articles

Pancreatic anti-GP2 and anti-Saccharomyces cerevisiae antibodies in ruminants with paratuberculosis: A better understanding of the immunopathogenesis of Crohn's disease

Ruminants (cattle and sheep) with Mycobacterium avium (MAP)-induced paratuberculosis (ptb), the ruminant model of Crohn's disease (CD), exhibit pancreatic specific autoantibodies (PAB) against GP2 but not against CUZD1. Since anti-Saccharomyces cerevisiae antibodies (ASCAs) is a CD marker, we tested MAP-infected ptb ruminants for ASCA, and compared them with ruminants lacking evidence of anti-MAP serology or with ruminants, which were positive for anti-GP2 antibodies. A total of 98 samples from ruminants (48 cattle and 50 sheep) were studied. IgG anti-MAP antibodies, and CD-related ASCA and anti-GP2 antibodies were tested by modified ELISAs. Nine cattle (18.75%) and 20 sheep (40%) were suffered from ptb. ASCA antibodies were present in 21/48 (43.7%) cattle and 10/50 (20%) sheep while anti-GP2 antibodies were present in 14/48 (29.2%) cattle, and 8/50 (16%) sheep. ASCA antibodies were more prevalent in anti-MAP antibody positive (14/29, 48.3%) than in anti-MAP negative ruminants (17/69, 24.6%, P=0.022) and also in anti-GP2 antibody positive (13/23, 56.5%) than in anti-GP2 negative ruminants (18/75, 24%, P=0.003). No association between ASCA and anti-MAP antibody concentrations were found (r=0.159, P=0.117). A significant association between ASCA and anti-GP2 antibody concentration were observed (r=0.211 and P=0.037). ASCA are present in a significant proportion of ruminants with ptb and correlate with anti-GP2 antibody positivity, a finding further supporting the notion that Crohn's disease and ptb share common immunological mechanisms of antigen-driven loss of self-tolerance.

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.

Antibodies to Crohn's disease peptide 353 as a diagnostic marker for pediatric Crohn's disease: a prospective multicenter study in Japan.

Various serologic markers such as anti-glycoprotein 2 antibodies and anti-Saccharomyces cerevisiae antibodies have been reported to be diagnostically useful in Crohn's disease. Mitsuyama et al. reported that antibodies to Crohn's disease peptide 353, a newly proposed serologic marker, were more useful in Japanese adults than anti-Saccharomyces. We addressed the same issue in Japanese children and adolescents. Prospectively enrolled subjects under 17years old assessed and treated at 12 pediatric centers in Japan included groups with Crohn's disease, ulcerative colitis, other intestinal diseases, or good health. The 3 serum markers were analyzed by enzyme-linked immunosorbent assays. Enrolled subjects, numbering 367, included 120 with Crohn's disease, 148 with ulcerative colitis, 56 with other intestinal diseases, and 43 healthy subjects. In Crohn's disease, anti-Crohn's disease peptide 353, anti-glycoprotein 2, and anti-Saccharomyces concentrations (median, 2.25, 3.0, and 8.9 U/mL) were significantly greater than in ulcerative colitis (1.1, 1.9, and 3.4; all P < 0.001), other intestinal diseases (1.1, 1.85, and 2.95; all P < 0.001), and healthy controls (1.1, 1.7, and 2.8; all P < 0.001), respectively. At 95% specificity, sensitivity of anti-Crohn's disease peptide (45.0%) was significantly higher than for anti-glycoprotein 2 (30.8%; P < 0.05) or anti-Saccharomyces (26.7%; P < 0.01). Anti-Crohn's disease peptide 353 proved more useful for diagnosis of Crohn's disease in Japanese children than the other 2 markers. To our knowledge, this is the first pediatric report to that effect.

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.

Assessing the ecological role of yeasts in the human gut

Background: The influence of gut microorganisms in health and disease is well documented, however, the role of yeasts has not been as widely studied as bacteria, despite associations with gastrointestinal disorders, such as Irritable Bowel Syndrome (IBS). For instance, Candida albicans is an opportunistic pathogen that has been linked to gastrointestinal symptoms. Methods: Urine, stool and blood samples will be collected from 40 healthy controls, 40 IBS and 40 inflammatory bowel disease (IBD) patients for microbial and metabolic analysis using primarily flow cytometry-fluorescence in situ hybridisation (FC-FISH) and proton nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Calprotectin and anti-Saccharomyces cerevisiae antibodies (ASCA) levels will assess gastrointestinal inflammation. Statistical analysis will identify yeasts and their metabolites associated with the cohorts of interest. Preliminary results: Preliminary tests to assess the presence and functionality of yeasts in healthy and IBS faecal samples using in vitro batch culture fermentation highlighted significant metabolic differences between the phenotypes: Trimethylamine (TMA), short chain fatty acids (SCFA) and ethanol predominantly distinguished in the IBS metabolic profile, compared to gamma-amino-N-butyrate (GABA) in the healthy donor. The addition of C. albicans shifted the healthy phenotype to resemble the IBS donor, whereas nystatin shifted the IBS phenotype towards the healthy metabolic profile. Conclusion: This study will further define the preliminary results that indicate the implication of yeasts in IBS pathogenesis. Understanding the role of yeasts within the healthy and diseased human gut is necessary to develop targeted therapies to improve patient’s quality of lives and relieve burdens on the economy and healthcare systems.

Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis.

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P=0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.

Anti-Saccharomyces cerevisiae Antibodies as a Prognostic Biomarker in Children With Crohn Disease.

Although anti-Saccharomyces cerevisiae antibodies (ASCAs) could be a useful biomarker in differentiating Crohn disease (CD) from ulcerative colitis (UC), their role as prognostic markers in children with CD has been underinvestigated. This longitudinal prospective observational study aimed to assess the prognostic value of ASCA status among children with CD managed using biologics. The study population comprised children with inflammatory bowel disease diagnosed with CD from 2012 to 2018. Cox regression model with adjustment for a priori covariates was used to examine the response to anti-tumor necrosis factor (TNF) biological therapy among ASCA-positive patients in comparison to ASCA-negative patients. There were 273 measurements available from the study cohort comprising children with CD, who were followed up for a median duration of 14 months (interquartile range 5-42). ASCA-positive patients had a higher risk for moderate to severe clinical disease (odds ratio 2.88; 95% confidence interval [CI] 1.2-7.55) and extensive endoscopic distribution (odds ratio 3.30; CI 1.12-9.74) at baseline in comparison to ASCA-negative patients, respectively. In comparison to ASCA immunoglobulin G (IgG)-negative patients, ASCA IgG-positive patients who were treated with biologics had a significantly lower relapse rate (adjusted hazard ratio 0.12; CI 0.02-0.93). Ten (14%) patients had an unstable ASCA value with either ASCA immunoglobulin A or ASCA IgG status changing from positive to negative or vice versa. ASCA-positive children with CD present with more extensive (endoscopic) and clinically severe disease. ASCA IgG is a useful prognostic marker among children with CD who receive biologics.

Antibodies to Brewer's Yeast in Rheumatoid Arthritis.

Antibodies to brewer’s yeast or anti-Saccharomyces cerevisiae antibodies (ASCA) have been detected in 70% of patients with Crohn’s disease and have become a part of the evaluation of a patient for Crohn’s disease. Prior evaluation of these antibodies in rheumatoid arthritis have been inconsistent. In an initial small study, the levels of antibodies were elevated but not statistically significant. In a second large study from China, 40% of rheumatoid arthritis patients were positive for immunoglobulin A (IgA) ASCA and 20% positive for immunoglobulin G (IgG) ASCA.Our study was inspired by the observation that several seronegative patients with rheumatoid arthritis were positive for ASCA antibodies. Between January 1, 2016 and January 1, 2018, a total of 241 patients with clinical rheumatoid arthritis were evaluated for antibodies to IGA and IGG ASCA, rheumatoid factor, cyclic citrullinated peptide (CCP), and antinuclear antibody (ANA). Our results indicate that 158 (66%) of these patients were positive for ASCA; 70 (29%) of these patients were positive for ASCA but negative for other serologies; 62% of the patients were positive for rheumatoid factor. Our results also indicate that the percentage of rheumatoid factor (95%) and CCP positive (78%) patients in the ASCA negative group was higher than the percentage of rheumatoid factor positive (49%) and CCP positive (37%) patients in the ASCA positive group, suggesting serologic differences between the two groups. Only 4% of the rheumatoid patients were negative for all the evaluated serologies.The possible role of mannan, a mucopolysaccharide from the cell wall of Saccharomyces cerevisiae (S. cerevisiae) in producing rheumatoid arthritis is discussed.

Celiac-Related Autoantibodies and IL-17A in Bulgarian Patients with Dermatitis Herpetiformis: A Cross-Sectional Study.

Background and objectives: Dermatitis herpetiformis (DH) is a blistering dermatosis, which shares common immunologic features with celiac disease (CD). The aim of the present study was to explore the performance of a panel of CD-related antibodies and IL-17A in Bulgarian patients with DH. Materials and Methods: Serum samples from 26 DH patients at mean age 53 ± 15 years and 20 healthy controls were assessed for anti-tissue transglutaminase (anti-tTG), anti-deamidated gliadin peptides (anti-DGP), anti-actin antibodies (AAA), and IL-17A by enzyme linked immuno-sorbent assay (ELISA), as well as anti-tTG, anti-gliadin (AGA), and anti-Saccharomyces cerevisiae antibodies (ASCA) using immunoblot. Results: The average serum levels of anti-tTG, anti-DGP, AGA, AAA, and the cytokine IL-17A were at significantly higher levels in patients with DH compared to the average levels in healthy persons which stayed below the cut-off value (p < 0.05). Anti-DGP and anti-tTG antibodies showed the highest diagnostic sensitivity and specificity, as well as acceptable positive and negative predictive value. None of the healthy individuals was found positive for the tested antibodies, as well as for ASCA within the DH group. All tests showed good to excellent correlations (r = 0.5 ÷ 0.9, p < 0.01). Conclusions: Although the diagnosis of DH relies on skin biopsy for histology and DIF, serologic testing of a panel of celiac-related antibodies could be employed with advantages in the diagnosing process of DH patients. Furthermore, DH patients who are positive for the investigated serologic parameters could have routine monitoring for gastrointestinal complications typical for the gluten-sensitive enteropathy.

Fungal Translocation Is Associated with Immune Activation and Systemic Inflammation in Treated HIV.

The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls. We measured serum levels of β-D-glucan (BDG) and anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulin G (IgG) and immunoglobulin A (IgA) and markers of systemic inflammation and immune activation in virally suppressed PLWH on antiretroviral therapy (ART) and uninfected controls. T-test and Mann-Whitney tests were used to compare markers by HIV status and correlation and regression analyses were used to assess associations of fungal translocation markers with markers of inflammation. One hundred seventy-six participants were included (128 HIV+ and 48 HIV-); 72% male, 65% African American, median age was 50 years, and CD4 was 710 cells/cm3. Levels of BDG tended to be lower in HIV+ when compared with controls (p = .05). No significant difference in levels of ASCA IgG and IgA was seen between groups (p > .75). There was a significant correlation between BDG and several markers of inflammation and immune activation in PLWH, not seen in uninfected controls. In contrast, no correlations were seen between levels of ASCA IgG and IgA with inflammatory markers. PLWH on ART do not have higher levels of BDG or ASCA when compared with uninfected controls, however, the association found between BDG and several inflammation markers suggests a potential role of fungal translocation in the heightened immune activation seen in treated HIV.

Gut permeability and mimicry of the Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) as potential mechanisms related to a subgroup of people with schizophrenia with elevated antigliadin antibodies (AGA IgG)

About one third of people with schizophrenia have elevated IgG antibodies to gliadin (AGA IgG) and increased inflammation. Understanding the mechanism by which this immune response occurs is critical to the development of personalized treatments. We examined gut permeability and mimicry to the glutamate receptor as possible mechanisms related to high gliadin antibodies (AGA IgG) seen in some people with schizophrenia. The Glutamate Ionotropic Receptor NMDA type Subunit Associated with protein 1 (GRINA) has a similar protein structure to gliadin representing a potential target for cross reactivity or mimicry. In a population of schizophrenia subjects (N = 160) and healthy controls (N = 80) we analyzed serum samples for both GRINA and Anti-Saccharomyces Cerevisiae antibodies (ASCA), related to gut permeability. Schizophrenia patients compared to controls had a higher prevalence of positivity to ASCA IgA (p = 0.004) and IgG (p < 0.001). Multinomial logistic regression showed an association between AGA IgG and ASCA IgG in schizophrenia (p = 0.05 for the estimated regression coefficient) but not in healthy controls (p = 0.13). GRINA IgG was higher in schizophrenia patients than in healthy controls (0.43 ± 0.30 vs. 0.22 ± 0.24, p < 0.001). Logistic regressions showed an association between AGA IgG and GRINA IgG in schizophrenia (p = 0.016 for the estimated regression coefficient) but not for the controls (p = 0.471). Thus, we propose that mimicry through the presence of cross-reactivity between gliadin and GRINA might disrupt the functions of the glutamate system and relate to illness pathophysiology in those with schizophrenia and elevated AGA IgG.

Elevated faecal calprotectin is linked to worse disease status in axial spondyloarthritis: results from the SPARTAKUS cohort.

To examine faecal calprotectin (F-calprotectin) levels and presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and their associations with disease subtype and current status in axial SpA (axSpA). F-calprotectin and ASCA in serum were compared between consecutive patients with a clinical axSpA diagnosis, classified as non-radiographic axSpA (nr-axSpA; n = 40) or AS (n = 90), and with healthy controls (n = 35). Furthermore, standard axSpA outcome measures were compared between axSpA patients (nr-axSpA and AS combined) with elevated vs normal F-calprotectin, ASCA IgA and IgG, respectively. Elevated F-calprotectin (⩾50 mg/kg) was observed in 27% of nr-axSpA patients, 38% of AS patients and 6% of controls. F-calprotectin was significantly higher in AS vs nr-axSpA [AS: geometric mean 41 (95% CI 32, 54) mg/kg; nr-axSpA: 24 (95% CI 16, 38) mg/kg; P = 0.037], and in each axSpA subtype vs controls. Overall, worse disease activity and physical function scores were observed among axSpA patients with elevated vs normal F-calprotectin levels, with significant differences regarding patient's visual analogue scale for global health, ASDAS using CRP, and BASFI (adjusted for age, sex, NSAID use, anti-rheumatic treatments, and CRP). ASCA titres and seropositivity (⩾10 U/ml) were similar in nr-axSpA (IgA/IgG-seropositivity: 8%/26%) and AS (7%/28%), and clinical outcome measures did not differ between patients with elevated vs normal ASCA IgA or IgG, respectively. Compared with controls (IgA/IgG-seropositivity: 0%/17%), ASCA IgA was significantly higher in both axSpA subtypes, and IgG was significantly higher in the AS group. In patients with axSpA, gut inflammation measured by elevated F-calprotectin is associated with worse disease activity and physical function, and may be a marker of more severe 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.

Starch Consumption May Modify Antiglycan Antibodies and Fecal Fungal Composition in Patients With Ileo-Anal Pouch.

Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.

Differential diagnosis of Crohn's disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae.

Glycoprotein 2 (GP2), the major autoantigen of Crohn's disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.

Isolated Small Bowel Crohnʼs Disease Diagnosed by Retrograde Eneteroscopy

Crohn's disease (CD) can occur through the entire gastrointestinal tract and in some instance can cause isolated small bowel disease which can present a diagnostic challenge A 47-year-old gentleman with history of diabetes mellitus that presented with one-month history of chronic watery non-bloody diarrhea with mild diffuse crampy abdominal pain, weight loss and progressively worsening bilateral lower limb edema and abdominal distention. He had no fever, nausea, vomiting, tenesmus or hematochezia. Examination was evident of mild diffuse abdominal tenderness with generalized anasarca. Laboratory work showed severe hypoalbuminemia with albumin of 1.9 mg/dl. Other chemistries and electrolytes were normal. He was HIV negative and stool cultures, parasitology and cryptosporidium were repeatedly negative. CT abdomen and pelvis showed diffuse small bowel wall thickening from the level of the distal jejunum to the terminal ileum with mesenteric adenopathy. Upper endoscopy and colonoscopy with terminal ileum intubation showed few gastric erosions with mild edematous colonic mucosa and no evidence of terminal ileum disease. Multiple gastric and colonic biopsies were unrevealing with negative viral, fungal and AFB cultures. He was discharged with close clinic follow up pending protein losing enteropathy workup that revealed positive fecal fat and positive anti-Saccharomyces cerevisiae antibodies. He presented 3 months later after missing clinic appointments, with similar complaint and with same lab and CT findings. Given unrevealing previous endoscopies, video capsule endoscopy was deployed showing multiple small bowel ulcers at about 63% length of small bowel with skip areas and possible strictures. Retrograde single balloon enteroscopy showed multiple medium to large size ulcers in the ileum starting at 20-25 cm from the ICV, the largest and more proximal ulcer seen appeared circumferential causing some narrowing of the lumen. Multiple biopsies were obtained showing mixed inflammatory infiltrate. Immunohistochemistry for lymphoma and special stains and cultures for AFB and fungi were negative He was discharged on oral prednisone with improvement of his symptoms on subsequent visit. Isolated small bowel involvement may be seen in up to 30% of patients with CD, making it more challenging to diagnose with routine small bowel imaging techniques. Enteroscopy and video capsule endoscopy has proven to be useful in diagnosis of isolated small bowel involvement3003_A Figure 1. Retrograde single balloon enteroscopy showed multiple medium to large size ulcers in the ileum3003_B Figure 2. CT abdomen and pelvis showed diffuse small bowel wall thickening from the level of the distal jejunum to the terminal ileum with mesenteric adenopathy. Arrows: Bowel wall thickness3003_C Figure 3. Video capsule endoscopy was deployed showing multiple small bowel ulcers at about 63% length of small bowel with skip areas and possible strictures

Diagnostic utility of serological biomarkers in patients with Crohn's disease: A case-control study.

The aim of this study was to examine the expression of serological markers in patients with inflammatory bowel disease in China, and determine the diagnostic utility of serological markers, individually and in combination, for the diagnosis and differential diagnosis of Crohn's disease (CD).Serum samples were obtained from 160 participants in Eastern China. Among the participants, 98 were diagnosed with CD, 33 had ulcerative colitis (UC), and 29 were healthy controls (HC). The serum samples were tested for the presence of antibodies against outer membrane porin C (anti-OmpC), Pseudomonas fluorescens bacterial sequence I2 (anti-I2), anti-laminarin (anti-L), anti-chitin (anti-C), anti-chitobioside carbohydrate antibody (ACCA), anti-laminaribioside carbohydrate antibody (ALCA), anti-mannobioside carbohydrate antibody (AMCA), and anti-Saccharomyces cerevisiae antibody (ASCA) by indirect enzyme-linked immunosorbent assay (ELISA).Individually, anti-C, anti-L, ASCA-IgG, and ALCA lacked diagnostic value in the differentiation of CD. ASCA-IgA remained the most accurate marker for the diagnosis of CD, with an area under the curve (AUC) of 0.77; however, its sensitivity and specificity were both lower than 75%. Among the combinations of the 5 markers with significant diagnosing ability for CD, combinations with any 2 of the 3 markers, ASCA IgA, AMCA, and ACCA positive, provided the best accuracy in the diagnosis and differential diagnosis of CD (sensitivity and specificity both above 75%) and had the highest Youden index.Serological antibodies, when considered in combination, have remarkable value in the diagnosis and differential diagnosis of CD. Especially, the combination of any 2 of the 3 markers, ASCA-IgA, AMCA, ACCA positive, appears to be optimal.

Altered uric acid metabolism in isolated colonic Crohn's disease but not ulcerative colitis.

Patients with inflammatory bowel disease (IBD) have higher incidence of developing nephrolithiasis. Increased uric acid production induced by Saccharomyces cerevisiae exacerbates colitis in mice. We aimed to evaluate the association between serum uric acid level and disease activity in IBD population. Four hundred and thirty-five patients enrolled in Jinling Hospital from January 1, 2015 to August 31, 2017 were included in the retrospective study. Clinical parameters were collected and compared with non-IBD matched controls (n=51). Serum uric acid to creatinine ratio (UA/Cr) was used as a biomarker for uric acid metabolism. Sixty-five active IBD patients were longitudinally studied to investigate the UA/Cr before and after therapy. Linear mixed models were estimated for Crohn's disease (CD) group to explore the relationship between UA/Cr and other parameters. Uric acid to creatinine ratio was significantly correlated with Crohn's disease activity index (ρ=0.184, P=0.002) and Harvey Bradshaw index (ρ=0.154, P=0.010) and C-reactive protein (ρ=0.591, P<0.001) in CD group. Colonic CD and anti-Saccharomyces cerevisiae antibody (ASCA) positive CD had an increased UA/Cr compared with L1, L3, and ASCA negative CD (P=0.027, P=0.0013, and P=0.043, respectively). A significant decrease in UA/Cr was observed after induction therapy in active CD (P=0.0002) but not in ulcerative colitis (P=0.076). Uric acid to creatinine ratio correlated with disease activity in CD. Colonic CD and ASCA positive CD had an increased UA/Cr. Effective treatment for CD patients lowered UA/Cr. Uric acid metabolism might be a novel aspect to investigate disease activity of IBD.

Late-Onset Crohn's Disease Is A Subgroup Distinct in Genetic and Behavioral Risk Factors With UC-Like Characteristics.

Age of onset is linked to variations in clinical phenotypes and natural history in Crohn's disease (CD). We aim to define etiologically more homogenous subgroups in CD based on ages of onset. We examined the distribution of CD polygenetic risk score (PRS) across ages of diagnosis in a Caucasian cohort of 2344 independent CD patients. We identified subgroups with a distinct distribution of PRS and compared those groups in genetics, demographic characteristics, clinical subphenotypes, and serological markers. The results were replicated in an independent cohort of 13,065 CD patients from the International Inflammatory Bowel Diseases Genetic Consortium (IIBDGC). We identified a late-onset (LO) subgroup in CD (age at diagnosis ≥ 55 years) with significantly lower PRS compared with the intermediate group (age at diagnosis between 5 and 55 years) in both cohorts. Smoking cessation, a risk factor for ulcerative colitis (UC) and protective factor for CD, had a higher rate in this LO subgroup in comparison with the intermediate group. We also compared the LO group with the intermediate group, and, consistent with previous reports, the LO group more often had colonic CD, had less penetrating disease behavior, and had less need for surgery. Serological analysis showed that LO CD patients were more antineutrophil cytoplasmic antibody positive and less antisaccharomyces cerevisiae antibody positive compared with the intermediate group. Variance component analysis indicated that overall genetic contribution to LO CD was lower relative to the middle group, and genetic heterogeneity testing indicated that LO CD was different from the middle group in underlying genetic architecture. Late-onset CD is subgroup distinct in genetic and behavioral risk factors with UC-like characteristics. 10.1093/ibd/izy148_video1izy148.video15791413461001.

Anti-High-Density Lipoprotein Antibodies and Antioxidant Dysfunction in Immune-Driven Diseases.

Impaired high-density lipoprotein (HDL) levels and antioxidant functionality of HDL, mainly attributed to a decreased paraoxonase-1 (PON1) functionality, have been described in autoimmune conditions. In this setting, a role for humoral response in cardiovascular disease is emerging. This study evaluates the role of immunoglobulin G (IgG) antibodies against HDL and disease-related autoantibodies on HDL dysfunction in immune-driven diseases. Serum IgG anti-HDL antibodies, PON1 activity, and total antioxidant capacity (TAC) were quantified in 381 patients with different immune-driven diseases [18 mixed connective tissue disease (MCTD), 35 primary Sjögren syndrome (pSS), 38 systemic sclerosis (SSc), 33 ANCA-associated vasculitis (AAV), 60 diabetes mellitus 1, 29 autoimmune B12 deficiency/pernicious anemia, 29 primary biliary cirrhosis, 46 IBD/Crohn, 54 IBD/UC, and 39 celiac disease (CD)] and 138 healthy controls. IgG anti-HDL antibodies were increased in MCTD, pSS, AAV, and inflammatory bowel disease (IBD) [Crohn and ulcerative colitis (UC)], even after correcting for total IgG levels, but not in organ-specific autoimmune diseases. Anti-HDL antibodies were negatively associated with PON1 activity in MCTD (r = -0.767, p < 0.001) and AAV (r = -0.478, p = 0.005), whereas both anti-HDL and anti-neutrophil cytoplasm antibod levels were related to an impaired PON1 activity and TAC in IBD/UC. In SSc, anti-centromere antibodies correlated PON1 activity. anti-Saccharomyces cerevisiae antibodies levels were negatively associated with PON1 activity (r = -0.257, p = 0.012) and PON1/TAC ratio (r = -0.261, p = 0.009) in IBD/Crohn. HDL dysfunction in CD was only related to anti-transglutaminase levels. IgG anti-HDL antibodies and HDL dysfunction are common hallmarks of systemic autoimmunity. Anti-HDL and disease-related autoantibodies account for the HDL antioxidant dysfunction in immune-driven conditions, mainly in systemic autoimmune disorders.