anti-Saccharomyces Cerevisiae Antibodies IgA Research Articles

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.

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.

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.

The Differences between Gluten Sensitivity, Intestinal Biomarkers and Immune Biomarkers in Patients with First-Episode and Chronic Schizophrenia.

Schizophrenia is a heterogeneous disorder without a fully elucidated etiology and mechanisms. One likely explanation for the development of schizophrenia is low-grade inflammation, possibly caused by processes in the gastrointestinal tract related to gluten sensitivity. The aims of this study were to: (1) compare levels of markers of gluten sensitivity, inflammation and gut permeability, and (2) determine associations between gluten sensitivity, inflammation, and intestinal permeability in patients with first-episode/chronic (FS/CS) schizophrenia and healthy individuals (HC). The total sample comprised 162 individuals (52 FS; 50 CS, and 60 HC). The examination included clinical variables, nutritional assessment, and serum concentrations of: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), anti-Saccharomyces cerevisiae antibody (ASCA), antigliadin antibodies (AGA) IgA/IgG, antibodies against tissue transglutaminase 2 (anti-tTG) IgA, anti-deamidated gliadin peptides (anti-DGP) IgG. A significant difference between groups was found in sCD14, ASCA, hs-CRP, IL-6 and AGA IgA levels. AGA IgG/IgA levels were higher in the FS (11.54%; 30.77%) and CS (26%; 20%) groups compared to HC. The association between intestinal permeability and inflammation in the schizophrenic patients only was noted. The risk for developing schizophrenia was odds ratio (OR) = 4.35 (95% confidence interval (CI 1.23–15.39) for AGA IgA and 3.08 (95% CI 1.19–7.99) for positive AGA IgG. Inflammation and food hypersensitivity reactions initiated by increased intestinal permeability may contribute to the pathophysiology of schizophrenia. The immune response to gluten in FS differs from that found in CS.

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.

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.

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.

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.

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.

Value of serological marker detection in hierarchical management of Crohn′s disease

Objective To explore the values of serological markers in the phenotype diagnosis of Crohn′s disease (CD). Methods From January 2015 to December 2016, 100 patients diagnosed as CD were enrolled. The levels of human anti-Saccharomyces cerevisiae antibody (ASCA) IgG, ASCA IgA, anti-mannobioside carbohydrate antibody (AMCA), anti-chitobioside carbohydrate antibody (ACCA), antibody against outer membrane porin C of Escherichia coli (anti-OmpC), antibody against pseudomonas fluorescens (anti-I2), flagella protein antibody, perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and antibodies to proteinase-3 (anti-PR3) were detected by indirect enzyme-linked immunosorbent assay (ELISA). Binary Logistic regression analysis was used to analyze the correlation between the serological markers and the phenotype of CD. The diagnosis values were evaluated by receiver operating characteristic (ROC) curve. Results The level of anti-I2 was significantly correlated with the narrow type of patients with CD (odd ratios (OR)=34.304, P=0.011); ACCA and flagella protein antibody were significantly correlated with the penetrating type of patients with CD (OR=1.024, P=0.027; OR=2.702, P=0.021). ASCA IgA and AMCA were significantly correlated with the lesion involved gastric, duodenum and small intestine in CD patients (OR=1.146, P=0.044; OR=1.035, P=0.013). In the diagnosis of narrow type CD, the diagnostic accuracy of anti-I2 was the highest (area under curve (AUC)=0.631, P=0.043), and according to this result, its best cutoff value was 0.650, and then the sensitivity increased to 28.6% (8/28). In the diagnosis of penetrating type CD, the diagnostic accuracy of flagella protein antibody was the highest (AUC=0.725, P<0.01). Anti-OmpC (AUC=0.677, P=0.006) and ACCA (AUC=0.644, P=0.025) also had higher diagnostic accuracy. According to these results, the best cutoff values of flagella protein antibody, anti-OmpC and ACCA were 0.395, 0.225 and 59.500, respectively, and then their sensitivity improved after correcting the cutoff values. The AUC of any one item positive in the combination of flagella protein antibody, anti-OmpC and ACCA in the diagnosis of penetrating type CD was 0.761 (P<0.01), which was significantly higher than the diagnostic accuracy of single antibody detection. In the diagnosis of the lesions involved gastric, duodenum and small intestine, the diagnostic accuracy of AMCA was the highest, and its AUC was 0.817 (P<0.01). ASCA IgA (AUC=0.772, P=0.001) and ACCA (AUC=0.752, P=0.001) also had higher diagnostic accuracy. The AUC of any one item positive of ASCA IgA and AMCA in the diagnosis of CD lesions involved gastric, duodenum and small intestine was 0.905 (P<0.01), which was significantly higher than the diagnostic accuracy of single antibody detection. The best cutoff values of ASCA IgA, AMCA and ACCA were 21.500, 55.000 and 29.500, respectively. And their sensitivity improved after correcting the cutoff values. The sensitivity of any one item positive in the three items also improved. Conclusion The detection of serological markers has great clinical values in the hierarchical management of phenotypes in Chinese CD population. Key words: Crohn disease; Enzyme-linked immunosorbent assay; Serological markers; CD phenotype

Clinical utility of serodiagnostic testing in pediatric inflammatory bowel disease

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

Anti-food and anti-microbial IgG subclass antibodies in inflammatory bowel disease

Objectives: Inflammatory bowel disease (IBD), particularly Crohn’s disease (CD), is associated with increased microbial-specific IgG and IgA antibodies, whereas alterations of anti-food antibodies are still disputed. The knowledge about IgG subclass antibodies in IBD is limited. In this study we analysed IgG subclass antibodies specific for nutritional and commensal antigens in IBD patients and controls.Methods: Serum IgG1, IgG2, IgG3 and IgG4 specific for wheat and milk extracts, purified ovalbumin, Escherichia coli and Bacteroides fragilis lysates and mannan from Saccharomyces cerevisiae were analysed by ELISA in patients with CD (n = 56), ulcerative colitis (UC; n = 29), acute gastroenteritis/colitis (n = 12) as well as non-inflammatory controls (n = 62).Results: Anti-Saccharomyces cerevisiae antibodies (ASCA) of all IgG subclasses and anti-B. fragilis IgG1 levels were increased in CD patients compared to UC patients and controls. The discriminant validity of ASCA IgG2 and IgG4 was comparable with that of ASCA pan-IgG and IgA, whereas it was inferior for ASCA IgG1/IgG3 and anti-B. fragilis IgG1. Complicated CD defined by the presence of perianal, stricturing or penetrating disease phenotypes was associated with increased ASCA IgG1/IgG3/IgG4, anti-B. fragilis IgG1 and anti-E. coli IgG1 levels. Anti-food IgG subclass levels were not different between IBD patients and controls and did not correlate with food intolerance. In contrast to anti-microbial Abs, food-specific IgG responses were predominately of the IgG4 isotype and all food-specific IgG subclass levels correlated negatively with age.Conclusion: Our study supports the notion that the adaptive immune recognition of food and commensal antigens are differentially regulated.

Diagnostic Potential of Zymogen Granule Glycoprotein 2 Antibodies as Serologic Biomarkers in Chinese Patients With Crohn Disease.

The need for reliable biomarkers for distinguishing Crohn disease (CD) from ulcerative colitis (UC) is increasing. This study aimed at evaluating the diagnostic potential of anti-GP2 antibodies as a biomarker in Chinese patients with CD. In addition, a variety of autoantibodies, including anti-saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibodies (PANCA), anti-intestinal goblet cell autoantibodies (GAB), and anti-pancreatic autoantibodies (PAB), were evaluated.A total of 91 subjects were prospectively enrolled in this study, including 35 patients with CD, 35 patients with UC, 13 patients with non-IBD gastrointestinal diseases as disease controls (non-IBD DC), and 8 healthy controls (HC). The diagnosis of IBD was determined based on the Lennard-Jones criteria, and the clinical phenotypes of the IBD patients were determined based on the Montreal Classification.Anti-GP2 IgG antibodies were significantly elevated in patients with CD, compared with patients with UC (P = 0.0038), HC (P = 0.0055), and non-IBD DC (P = 0.0063). The prevalence of anti-GP2 IgG, anti-GP2 IgA and anti-GP2 IgA, or IgG antibodies in patients with CD was 40.0%, 37.1%, and 54.3%, respectively, which were higher than those in non-IBD DC (anti-GP2 IgG, 15.4%; anti-GP2 IgA, 7.7%; and anti-GP2 IgA or IgG, 23.1%) and those in patients with UC (anti-GP2 IgG, 11.4%; anti-GP2 IgA, 2.9%; and anti-GP2 IgA or IgG, 14.3%). For distinguishing CD from UC, the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratios (LR+) were 40%, 88.6%, 77.8%, and 3.51 for anti-GP2 IgG, 37.1%, 97.1%, 92.9%, and 13.0 for anti-GP2 IgA, and 54.3%, 85.3%, 79.2%, and 3.69 for anti-GP2 IgA or IgG. For CD diagnosis, the combination of anti-GP2 antibodies with ASCA IgA increased the sensitivity to 68.6% with moderate loss of specificity to 74.3%. Spearman's rank of order revealed a significantly positive correlation of anti-GP2 IgG with ileocolonic location of disease (L3) (P = 0.043) and a negative correlation of anti-GP2 IgA with biologic therapy (P = 0.012).Our findings suggest that anti-GP2 antibodies could serve as a biomarker for distinguishing patients with CD from patients with UC, and the combination of anti-GP2 antibodies with ASCA IgA may improve the predictive power.

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.

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

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