anti-Saccharomyces Cerevisiae Antibodies IgG Research Articles

Prevalence of Anti- Saccharomyces Cerevisiae Antibodies (ASCA) in Patients With Irritable Bowel Syndrome (IBS). A Case-control Study.

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects patients' quality. Recent research has shown variations in the mycobiome of individuals with IBS, particularly involving Saccharomyces cerevisiae , and its association with dysbiosis and visceral hypersensitivity. However, the role of Anti-Saccharomyces cerevisiae antibodies (ASCA) in IBS remains unclear, despite their significance as markers of disease severity in inflammatory bowel disease. This study aimed to investigate the role of ASCA in Mexican IBS patients compared with healthy controls (HCs) and determine whether these antibodies could help differentiate between IBS patients and healthy individuals. Serum samples from 400 IBS patients and 400 HC were analyzed. ASCA IgG levels were measured using enzyme-linked immunosorbent assay (ELISA). The IBS patients were further categorized into subtypes: constipation predominant (IBS-C), diarrhea predominant (IBS-D), and mixed (IBS-M). Among the participants, 66 IBS patients (16.5%) and 63 HC (15.75%) tested positive for ASCA IgG. No significant difference was observed in ASCA IgG levels between the 2 groups ( P value: 0.8451). The prevalence of ASCA IgG positivity was 14.5% in IBS-C, 17.8% in IBS-D, and 15.9% in IBS-M. Surprisingly, a high prevalence of ASCA IgG was found in the HC group in Mexico. Furthermore, there was no significant difference in ASCA IgG levels between IBS patients and controls. These findings suggest that ASCA is not useful as a discriminatory biomarker for distinguishing IBS patients from healthy individuals and cannot serve as a surrogate marker for visceral hypersensitivity.

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.

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.

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.

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.

Anti-Saccharomyces cerevisiae Antibodies in Rheumatoid Arthritis.

This study was conducted to evaluate the frequency of anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with rheumatoid arthritis (RA). Eighty-three RA patients with positive anti-cyclic citrullinated antibodies (anti-CCP) and 160 healthy blood donors were included in this study. ASCA IgG and IgA were assessed with enzyme-linked immunosorbent assay. The frequency of ASCA was significantly higher in RA patients than in healthy subjects (22.9% vs 3.7%, P < 10-3). Both ASCA IgG and ASCA IgA were significantly more frequent in RA patients than in the control group (20.5% vs 3.1%, P < 10-3and 9.6% vs 0.6%, P = .002, respectively). ASCA IgG and ASCA IgA levels were significantly higher in RA patients than in healthy subjects (7.8 ± 8.4 U/mL vs 2.3 ± 2.8 U/mL, P < 10-6 and 6.2 ± 10.9 U/mL vs 3.4 ± 1.7 U/mL, P = .002, respectively). A high frequency of ASCA IgG and ASCA IgA has been found in RA patients.

CLASSICAL SEROLOGICAL MARKERS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE IN BRAZIL

Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCAs) have long been used to differentiate between Crohn's disease (CD) and ulcerative colitis (UC), more recently having been used as prognostic indicators. To determine the diagnostic accuracy of serological markers in the identification of pediatric CD and UC in Sao Paulo, Brazil, as well as to correlate those markers with characteristics demographic and clinical of these two diseases. Retrospective cross-sectional multi-center study involving pediatric patients with inflammatory bowel disease (IBD). We identified ASCAs serological markers and p-ANCA, correlating their presence with demographic and clinical data, not only in the patients with IBD but also in a group of age-matched gastrointestinal disease-free controls. A total of 122 patients, 74 with IBD (46% males), treated at four pediatric gastroenterology referral centers, the mean age of 13±7 years, 49 (66%) with CD, and 25 (34%) with UC. The control Group comprised 48 patients (54% males). The proportion of patients testing positive for p-ANCA was significantly higher in the UC group (69.9%) compared to the CD group (30.4%), as well as being significantly higher in the CD group versus the control Group (P<0.001 for both). The proportion of patients testing positive for ASCA IgA (76.2%) and ASCA IgG (94.4%) markers was also significantly higher in the CD group than in the control Group (P<0.001), and such positivity correlated significantly with the use of immunomodulatory medications such as azathioprine and anti-tumor necrosis factor agents (azathioprine 38.9%, anti-TNF 55.6%; P=0.002). In the CD group, the proportion of patients testing positive for the ASCA IgA was significantly higher among those who underwent surgery than among those who did not (26.86±17.99; P=0.032). In pediatric patients with IBD in Sao Paulo, Brazil, serological tests proving to be highly specific, although not very sensitive, for the diagnosis of IBD. However, the serological markers showed a positive correlation with the severity of the disease.

Detection of a novel antigen for Crohn’s disease

Background and aims Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease (IBD). We identify an antigen-like substance called Crohn's disease (CD) antibody binding polypeptide (CABP). As a serological marker, anti-CABP may contribute to the diagnosis of IBD. The present study aims to evaluate the clinical role of anti-CABP as a serological antibody for IBD. Methods Using enzyme-linked immunosorbent assay (ELISA), serum anti-CABP, anti-Saccharomyces cerevisiae antibody (ASCA) and perinuclear anti-neutrophil cytoplasmic antibody (pANCA), titers were tested in 168 CD patients, 123 ulcerative colitis (UC) patients and 170 controls. The correlation between serum antibody and clinical characteristics was investigated. The diagnostic potential of the anti-CABP was evaluated by receiver operating characteristic (ROC) analysis. Results The titers of anti-CABP (IgA or IgG) and ASCA IgG of CD patients were significantly higher than non-CD group (all p < .01). In the differential diagnosis of CD and non-CD, anti-CABP IgA revealed an area under the curve (AUC) of 0.706 and anti-CABP IgG demonstrated an AUC of 0.788. As an individual antibody, anti-CABP could effectively distinguish CD from non-CD (AUC 0.816), and the diagnostic efficacy was better than that of ASCA (AUC 0.680). The combined use of anti-CABP, ASCA and pANCA significantly improved the diagnostic value (AUC 0.857). Anti-CABP positive rates were associated with perianal lesions and disease location in CD patients (both p < .05). Conclusions Our results suggested that anti-CABP could be used as a serological marker to assist the diagnosis of CD. Clinical trial registration This trial is registered with clinical trial registration unique identifier ChiCTR2000037094.

Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity.

Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data is available on fungal dysbiosis in the children at the risk of type 1 diabetes (T1D). We hypothesized that the co-occurrence of fungal and bacterial dysbiosis contributes to the intestinal inflammation and autoimmune destruction of insulin-producing beta-cells in T1D. Fecal and blood samples were collected from 26 children tested positive for at least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) and matched autoantibody-negative children with HLA-conferred susceptibility to T1D (matched for HLA-DQB1 haplotype, age, gender and early childhood nutrition). Bacterial 16S and fungal ITS2 sequencing, and analyses of the markers of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses, the children were followed for development of clinical T1D (median 8 years and 8 months). Nine autoantibody positive children were diagnosed with T1D, whereas none of the autoantibody negative children developed T1D during the follow-up. Fungal dysbiosis, characterized by high abundance of fecal Saccharomyces and Candida, was found in the progressors, i.e., children with beta-cell autoimmunity who during the follow-up progressed to clinical T1D. These children showed also bacterial dysbiosis, i.e., increased Bacteroidales and Clostridiales ratio, which was, however, found also in the non-progressors, and is thus a common nominator in the children with beta-cell autoimmunity. Furthermore, the progressors showed markers of intestinal inflammation detected as increased levels of fecal HBD2 and ASCA IgG to fungal antigens. We conclude that the fungal and bacterial dysbiosis, and intestinal inflammation are associated with the development of T1D in children with beta-cell autoimmunity.

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

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 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.

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.

Antibodies against glycoprotein 2 display diagnostic advantages over ASCA in distinguishing CD from intestinal tuberculosis and intestinal Behçet's disease.

Objectives:There is an increasing need to identify reliable biomarkers for distinguishing Crohn’s disease (CD) from other gastrointestinal disorders sharing similar clinical and pathological features. This study aimed at evaluating the diagnostic potential of antibodies to zymogen granule glycoprotein GP2 (aGP2) in a large, well-defined Chinese cohort with a special focus on their role in discriminating CD from intestinal Behçet's disease (BD) and intestinal tubercolosis (ITB).Methods:A total of 577 subjects were prospectively enrolled, including 171 patients with CD, 208 patients with ulcerative colitis (UC), 71 with BD, 57 with ITB and 70 healthy controls (HC). aGP2 and anti-Saccharomyces cerevisiae antibodies (ASCA) were determined by ELISA. Perinuclear antineutrophil cytoplasmic antibodies were tested by indirect immunofluorescent assay.Results:aGP2 IgG and IgA levels were significantly elevated in patients with CD compared with those in patients with UC, intestinal BD, and ITB and HC. Conversely, ASCA IgG levels were not different between CD and intestinal BD patients, whereas ASCA IgA levels did not discriminate CD from intestinal BD and ITB patients. aGP2 IgA and IgG displayed a better assay performance (larger areas under the curve) over ASCA IgA and IgG in differentiating CD from disease controls (P<0.05). ASCA IgA did not discriminate CD from disease controls. aGP2 IgA and/or IgG was significantly associated with penetrating disease (B3) and ileal CD (L1) (P<0.05), whereas ASCA IgA and/or IgG was not.Conclusions:In comparison with ASCA, aGP2 distinguishes CD from intestinal BD or ITB as disease controls more efficiently, aiding in the differential diagnosis of IBD.

Anti-Saccharomyces cerevisiae antibodies (ASCA) are associated with body fat mass and systemic inflammation, but not with dietary yeast consumption: a cross-sectional study

BackgroundBaker’s/brewer’s yeast, Saccharomyces cerevisiae, has been used as an alternative to antibiotic growth promoters to improve growth performance in animals. In humans, Saccharomyces cerevisiae is among the most commonly detected fungi in fecal samples and likely originates from food. Recently, an association between anti-Saccharomyces cerevisiae antibodies (ASCA) and obesity in humans was suggested, but the cause of the elevated ASCA levels is not clear. Our aim was to study ASCA in morbidly obese subjects and explore potential associations with anthropometrics, diet, co-morbidities and biomarkers of inflammation and gut permeability.MethodsSubjects with morbid obesity referred to a specialized hospital unit were included. Diet and clinical data were recorded with self-administered questionnaires. Main dietary sources of baker’s/brewer’s yeast (e.g. bread and beer) were used as a proxy for the intake of yeast. Laboratory analyses included ASCA, serum zonulin (reflecting gut permeability), C-reactive protein and a routine haematological and biochemical screening.ResultsOne-hundred-and-forty subjects; 109 (78%) female, 98 with dietary records, mean age 43 years and BMI 42 kg/m2 were included. The number of ASCA positive subjects was 31 (22%) for IgG, 4 (2.9%) for IgA and 3 (2.1%) for IgM. Age, body fat mass and C-reactive protein were significantly higher in IgG-positive compared to IgG-negative subjects (P < 0.05). A borderline significant association was found between elevated zonulin and ASCA IgG-positivity (P = 0.06). No association was found between yeast-containing food and ASCA IgG-positivity, or between yeast-containing food and fat mass.ConclusionsThe findings indicate that ASCA IgG-positivity may be linked to the generalized inflammation commonly seen with increased adiposity, but not to dietary yeast intake. Other potential causes for the raised ASCA IgG concentrations, such as genetic predisposition, deviations in the gut microbiota and cross-reactivity of ASCA with other antigens, were not explored.

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.

Differential response to microbial antigens by age of diagnosis in patients with Crohn's disease.

PurposeFifteen percent of incident Crohn’s disease (CD) cases are diagnosed at older ages and demonstrate colonic location and inflammatory behavior. Serologic responses to gut microbial antigens are associated with specific phenotypes, and may differ by age at diagnosis. Our aim was to identify an association between age at diagnosis of CD and responses to gut microbial antigens.Patients and methodsLevels of anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulins A and G (IgA and IgG), antibodies to Escherichia coli outer membrane porin-C (anti-Omp-C), antibodies to clostridial flagellin (anti-CBir-1), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were compared in patients by age in three diagnosis groups: patients diagnosed at ages of <40, ≥40–59, and ≥60 years. For each antigen, patients with antibody levels in the first, second, third, and fourth quartile were assigned a score of 1, 2, 3, or 4, respectively. Individual scores were added to create a quartile sum score representing cumulative quantitative immune response.ResultsEighteen, 17, and 12 patients were diagnosed at ages <40, 40–59, and ≥60 years, respectively. The majority (71%) had ileocolonic disease in the youngest group, compared to 36% in the oldest group (P=0.001). Mean ASCA IgA and IgG titers were increased in the youngest age group compared to the older groups (P=0.19 and P=0.13, respectively). Mean quartile sum scores for antibody levels were 7.2±2.8 in those patients diagnosed at ages <40 years, 4.9±2.9 in the 40–59-year-old age group, and 5.6±2.6 in the ≥60-year-old age group (P=0.06).ConclusionA trend toward decreased cumulative immune responses to CD-associated gut antigens was observed in CD patients diagnosed at older ages compared to younger patients. Host responses to microbial antigens may be less important in older onset IBD and may contribute to the distinct phenotype in this group.

Anti-Saccharomyces cerevisiae antibody titres correlate well with disease activity in children with Crohn's disease.

The role of noninvasive biologic markers for disease activity is very important in children with Crohn's disease. The aim of this study was to assess an association between disease activity and quantitative serum anti-Saccharomyces cerevisiae antibody (ASCA) titres. Anti-Saccharomyces cerevisiae antibody immunoglobulin (Ig) A and immunoglobulin G titres, paediatric Crohn's disease activity index (PCDAI), serum albumin and C-reactive protein (CRP) were repeatedly measured simultaneously in children with Crohn's disease. A possible association between ASCA IgA and IgG titres and changes in PCDAI was examined. Serial 136 measurements of ASCA IgA and IgG titres were documented in 57 children with Crohn's disease over a mean duration of 3.1 ± 2.1 years. In a univariate linear regression model, there were significant correlations between ASCA IgA titres and PCDAI (p < 0.001), CRP (p <0.01) and low serum albumin (p < 0.001), respectively. Similarly, ASCA IgG titres significantly correlated with PCDAI, CRP and low serum albumin. Both ASCA IgA and IgG titres seemed to correlate well with clinical Crohn's disease activity in children. Measuring these antibodies may be considered during routine clinical care for those patients.

Distinct patterns of IgG and IgA against food and microbial antigens in serum and feces of patients with inflammatory bowel diseases.

BackgroundInflammatory bowel disease (IBD) is associated with a defective intestinal barrier and enhanced adaptive immune responses against commensal microbiota. Immune responses against food antigens in IBD patients remain poorly defined.MethodsIgG and IgA specific for food and microfloral antigens (wheat and milk extracts; purified ovalbumin; Escherichia coli and Bacteroides fragilis lysates; mannan from Saccharomyces cerevisiae) were analyzed by ELISA in the serum and feces of patients with Crohn's disease (CD; n = 52 for serum and n = 20 for feces), ulcerative colitis (UC; n = 29; n = 17), acute gastroenteritis/colitis (AGE; n = 12; n = 9) as well as non-inflammatory controls (n = 61; n = 39).ResultsSerum anti-Saccharomyces cerevisiae antibodies (ASCA) and anti-B. fragilis IgG and IgA levels were increased in CD patients whereas antibody (Ab) levels against E. coli and food antigens were not significantly different within the patient groups and controls. Subgroup analysis revealed that CD patients with severe diseases defined by stricturing and penetrating lesions have slightly higher anti-food and anti-microbial IgA levels whereas CD and UC patients with arthropathy have decreased anti-food IgG levels. Treatment with anti-TNF-α Abs in CD patients was associated with significantly decreased ASCA IgG and IgA and anti-E. coli IgG. In the feces specific IgG levels against all antigens were higher in CD and AGE patients while specific IgA levels were higher in non-IBD patients. Anti-food IgG and IgA levels did not correlate with food intolerance.SummaryIn contrast to anti-microbial Abs, we found only minor changes in serum anti-food Ab levels in specific subgroups of IBD patients. Fecal Ab levels towards microbial and food antigens show distinct patterns in controls, CD and UC patients.