Anti-chitobioside Carbohydrate Antibodies Research Articles

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.

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

The value of serum antibodies in differentiating inflammatory bowel disease, predicting disease activity and disease course in the newly diagnosed patient

Background: Data on serum antibodies in untreated adult inflammatory bowel disease (IBD) patients at diagnosis are scarcely available, and results on the stability of antibody presence over time are inconsistent. Our aim was to investigate antibodies in newly diagnosed, untreated IBD patients in relation to disease phenotype and course. Furthermore, we analyzed antibody presence over time.Methods: Baseline anti-Saccharomyces cerevisiae antibodies (ASCA), anti-chitobioside carbohydrate antibodies (ACCA), anti-laminaribioside carbohydrate antibodies (ALCA) and anti-mannobioside carbohydrate antibodies (AMCA) were measured with enzyme-linked immunosorbent assays and perinuclear anti-neutrophilic cytoplasmic antibodies (pANCA) was measured by indirect immunofluorescence in serum of 120 untreated IBD patients at diagnosis and 19 healthy controls. Antibodies were related to disease outcomes. Serial measurements were available in 71 patients.Results: The combination of pANCA and ASCA enabled good discrimination between UC and CD (p = .004). Antibody presence was relatively stable over time, even though there were significant changes in concentrations. There was a trend towards larger fluctuations in concentration with immunosuppressive medication. Baseline pANCA in UC patients correlated with calprotectin values (rho = .545, p = .019) and change in pANCA status over time was associated with disease activity at that moment. No associations were found with antibodies at diagnosis and disease outcomes.Conclusion: Antibody profiles at diagnosis support the distinction between CD and UC. Anti-glycan antibodies are reasonably stable over time, but may fluctuate under the influence of immunosuppressive treatment which may explain the inconsistency in findings hitherto. The appearance or disappearance of pANCA antibodies during follow-up correlated with disease activity in UC and may be used in disease monitoring.

Study on joint detection of serological markers in the diagnosis of Crohn's disease

Objective To explore the values of detecting anti-Saccharomyces cerevisiae antibody (ASCA) IgA,ASCA IgG,anti laminaribioside carbohydrate antibody (ALCA),anti-chitobioside carbohydrate antibody (ACCA) and anti mannobioside carbohydrate antibody (AMCA) and antibody against outer membrane porin C of Escherichia coli (anti-OmpC) in the diagnosis of Crohn's disease (CD).Methods From October 10th 2012 to January 24th 2013,63 patients diagnosed as CD were selected.At the same period 30 patients diagnosed as ulcerative colitis (UC) were set as disease control group and 25 individuals without abnormal findings under endoscope and imaging examination were set as healthy control group.Fasting blood of all the subjects were drawn in the morning and serum was isolated after centrifuge.The level of ASCA IgG,ALCA,AMCA,ACCA,ASCA IgA,anti OmpC and I2 was detected by indirect enzyme linked immunosorbent assay.The sensitivity,specificity,positive predictive value and negative predictive value of each antibody were calculated and its value in the diagnosis was evaluated by receiver operating characteristic (ROC) curve.Results In the differential diagnosis of CD and UC by single antibody test,the accuracy of AMCA was the highest and the area under ROC curve was 0.739.In the screening of CD with single antibody examination,the diagnosis accuracy of I2 antibody was the highest and the area under ROC curve was 0.751.In multi antibodies joint examination,the accuracy of either ASCA IgA or AMCA positive was the highest in the differential diagnosis of CD and UC,also in the screening of CD and the area under ROC curve was 0.612 and 0.633,respectively.Conclusion In clinical practice,CD screening and the differential diagnosis of CD and UC may be achieved through detecting AMCA,ASCA IgA and I2 antibody. Key words: Crohn disease; Antibodies; Enzyme-linked immunosorbent assay; Serological markers; Diagnosis

Readressing the Role of Toll-Like Receptor-4 Alleles in Inflammatory Bowel Disease: Colitis, Smoking, and Seroreactivity

Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001). The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.

Serum anti-glycan antibody biomarkers for inflammatory bowel disease diagnosis and progression: A systematic review and meta-analysis

Anti-glycan antibody serologic markers may serve as a useful adjunct in the diagnosis/prognosis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis/systemic review aimed to evaluate the diagnostic value, as well as the association of anti-glycan biomarkers with IBD susceptible gene variants, disease complications, and the need for surgery in IBD. The diagnostic odds ratio (DOR), 95% confidence interval (CI), and sensitivity/specificity were used to compare the diagnostic value of individual and combinations of anti-glycan markers and their association with disease course (complication and/or need for surgery). Fourteen studies were included in the systemic review and nine in the meta-analysis. Individually, anti-Saccharomyces cervisiae antibodies (ASCA) had the highest DOR for differentiating IBD from healthy (DOR 21.1; 1.8-247.3; two studies), and CD from UC (DOR 10.2; CI 7.7-13.7; seven studies). For combination of ≥2 markers, the DOR was 2.8 (CI 2.2-3.6; two studies) for CD-related surgery, higher than any individual marker, while the DOR for differentiating CD from UC was 10.2 (CI 5.6-18.5; three studies) and for complication was 2.8 (CI 2.2-3.7; two studies), similar to individual markers. ASCA had the highest diagnostic value among individual anti-glycan markers. While anti-chitobioside carbohydrate antibody (ACCA) had the highest association with complications, ASCA and ACCA associated equally with the need for surgery. Although in most individual studies the combination of ≥2 markers had a better diagnostic value as well as higher association with complications and need for surgery, we found the combination performing slightly better than any individual marker in our meta-analysis.

Antiglycan Antibodies in Greek Patients with Inflammatory Bowel Disease

Antiglycan antibodies have recently been reported to be associated with Crohn's disease (CD). These antibodies include anti-Saccharomyces cerevisiae mannan antibodies (ASCA), anti-laminariobioside carbohydrate antibodies (ALCA), anti-chitobioside carbohydrate antibodies (ACCA), and anti-mannobioside carbohydrate antibodies (AMCA). The aim of this study was to evaluate their diagnostic accuracy in Greek patients with inflammatory bowel disease (IBD). Serum was collected from 191 patients with IBD (85 with ulcerative colitis (UC) and 106 with CD), 29 cases with other causes of intestinal inflammation and 96 healthy controls. Antiglycan antibodies were measured using commercially available enzyme immunoassays. Higher levels of antiglycan antibodies were detected in patients with CD compared to patients with UC and controls. Although all types of antiglycan antibodies had a high specificity for diagnosing CD, their sensitivity was rather low, with best results obtained with ASCA and ALCA (41.5 and 52.8%, respectively). Increased levels of ASCA and ALCA were associated with stricturing and penetrating disease phenotype, and the need for surgery (p < 0.05). Antiglycan antibodies in Greek IBD patients are significantly associated with CD, and especially to phenotypes of complicated disease, with ASCA and ALCA exhibiting the highest sensitivity.

Anticarbohydrate antibodies as markers of inflammatory bowel disease in a Central European cohort

The study discusses the role of antichitobioside carbohydrate antibody (ACCA), antilaminaribioside carbohydrate antibodies (ALCA), and antimannobioside carbohydrate antibodies (AMCA) in Central European patients with inflammatory bowel disease (IBD). Twohundred and seventy-two serum samples were used - 116 Crohn's disease (CD), 84 ulcerative colitis, and 72 healthy control samples. All samples were evaluated using enzyme-linked immunosorbent assay for the following four anticarbohydrate assays: ACCA, ALCA, AMCA, and anti-Saccharomyces cerevisiae antibodies (gASCA). gASCA antibodies showed the highest sensitivity (67%) for a CD diagnosis, followed by AMCA (31%), ACCA (27%), and ALCA (25%). Positivity of at least one of the four assays increased the overall sensitivity of antibody testing in CD up to 85.5%. Mean serum gASCA levels were significantly higher in CD patients who were younger at diagnosis and had a longer disease duration before blood sampling (P<0.001). In nonstricturing, nonpenetrating CD, serum gASCA levels were lower than in patients with stricturing and/or penetrating behavior (P<0.05). The strongest association of gASCA was found with ileocolonic CD and with upper gastrointestinal disease (P<0.001). No association between anticarbohydrate (AMCA, ACCA, and ALCA) antibodies and CD location, behavior, age at onset, and disease duration was found; however, that sample size of some of our subgroups was probably too small to make firm conclusions on associations with all CD phenotypes. None of the assessed anticarbohydrate assays was predictive of colonic CD in patients in whom the distinction between CD and ulcerative colitis is not obvious using routine diagnostic methods. There was no relationship between the presence or concentration of anticarbohydrate antibodies and the inflammation measured by C-reactive protein levels. The use of a panel of anticarbohydrate antibodies may provide additional help in distinguishing IBD from non-IBD disease patterns. The addition of AMCA, ALCA, and ACCA assays as IBD serology markers improves the overall sensitivity of immunological examinations in IBD; however, anticarbohydrate assays are not helpful for predicting CD behavior.

Les marqueurs sérologiques des maladies inflammatoires chroniques intestinales (MICI)

To date, anti-Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic autoantibodies known as NANA are still the paramount serological markers of IBD. They are relevant for their predictive value to discriminate indeterminate colitis, but also for their prognostic value and more recently observed, for their correlation with disease phenotypes especially in Crohn's disease. This article also gives an overall picture of the others IBD serological markers such as antibodies to exocrine pancreas, and more recently discovered antimicrobial antigens antibodies (such as anti-Escherichia coli outer membrane porin or OmpC, anti-Pseudomonas fluorescens or I2, anti-CBir1 flagellin-derived protein, anti-Bacteroides caccae OmpW, anti-Mycobacterium avium subspecies paratuberculosis or MAP) and antiglycan antibodies (such as antilaminaribioside carbohydrate antibody or ALCA, antichitobioside carbohydrate antibody or ACCA and antimannobioside carbohydrate antibody or AMCA). Les marqueurs de référence de dépistage des MICI restent à ce jour les anticorps anti-Saccharomyces cerevisiae (ASCA) et les ANCA atypiques de type NANA. Leur intérêt réside également dans leur valeur prédictive dans les colites indéterminées, dans leur valeur pronostique au cours des MICI et plus récemment dans leur association à des phénotypes particuliers, notamment dans la maladie de Crohn. Cet article fait également le point sur la place des autres marqueurs des MICI dont les anticorps antipancréas exocrine et des marqueurs plus récents comme les anticorps anti-antigènes microbiens (antiporine OmpC de l’Escherichia coli, antiséquence I2 du Pseudomonas fluorescens, antiprotéine CBir1 dérivée de la flagelline, anti-OmpW du Bacteroides caccae, anti-MAP pour Mycobacterium avium subspecies paratuberculosis) et les anticorps antiglycans (antimannobioside, antilaminaribioside et antichitobioside).

Development of pouchitis following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis: A role for serological markers and microbial pattern recognition receptor genes

Background and Aims Pouchitis, the most common complication after proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, has been attributed to altered composition of faecal flora. We investigated the role of antimicrobial and antiglycan antibodies and polymorphisms in microbial pattern recognition receptor genes. Methods Clinical charts of all 184 patients with ulcerative colitis who underwent IPAA between 1990–2004 were reviewed for pre- and post-operative disease course. Results Follow-up data were available in 172 patients [67 female, median age at proctocolectomy 39.1 years]. During a median follow-up of 6.7 (interquartile range 3.7–10.5) years, 80 patients (47%) developed at least one episode of pouchitis. Cox proportional-hazard regression identified extra-intestinal manifestations [HR 1.78 (95%CI 1.10–2.88), p = 0.020], a GT/TT genotype at Toll-like-receptor-1 S87I [HR 1.64 (1.01–2.66), p = 0.047], anti-chitobioside carbohydrate antibodies [HR 2.03 (1.11–3.70), p = 0.021] and young age at diagnosis [ p = 0.003] to be independently associated with pouchitis. Factors associated with chronic pouchitis, diagnosed in 33 patients (19%), were extra-intestinal manifestations [HR 2.45 (1.07–5.62), p = 0.034], backwash ileitis [HR 3.15 (1.10–9.00), p = 0.032], outer-membrane porin antibodies [HR 2.67 (1.20–5.94), p = 0.016] and young age at proctocolectomy [ p = 0.008]. Conclusions: The reported association with antibodies and Toll-like-receptor-1 supports the pathophysiological role of the faecal flora in the development of pouchitis.

Novel anti-carbohydrate autoantibodies in patients with inflammatory bowel disease: Are they useful for clinical practice?

The objective of this study was to test the diagnostic accuracy of novel anti-carbohydrate assays in patients with inflammatory bowel disease, namely in Crohn's disease. These carbohydrate assays are based on oligosaccharide chitobioside carbohydrate - anti-chitobioside carbohydrate antibodies (ACCA), laminaribioside carbohydrate anti-laminaribioside carbohydrate antibodies (ALCA), and mannobioside carbohydrate - anti-mannobioside carbohydrate antibodies (AMCA). We compared these assays with the anti-Saccharomyces cerevisiae antibodies (ASCA) assay. The results of this study suggest that ASCA are still the best serological marker for Crohn's disease. Further studies are required to explore the clinical utility of ACCA, ALCA and AMCA.

Relevance of serologic studies in inflammatory bowel diseases

The panel of serologic markers for inflammatory bowel diseases (IBDs) is rapidly expanding. Although anti- Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (atypical P-ANCA) remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. Such antibodies include anti-OmpC (outer membrane porin C), anti- Pseudomonas fluorescens (anti-I2) and antiglycan antibodies (anti-laminaribioside carbohydrate antibody [ALCA]), anti-chitobioside carbohydrate antibody [ACCA]), anti-mannobioside carbohydrate antibody [AMCA]) and anti-CBir1; this latter is the first bacterial antigen to induce colitis in animal models of IBD and also leads to a pathological immune response in IBD patients (anti-flagellin antibody). The role of assessment of various antibodies in the current diagnostic algorithm of IBD is rather questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is getting more into the focus of interest. An increasing number of observations confirm that patients with Crohn's disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titer of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.

Antibodies Against Laminaribioside and Chitobioside Are Novel Serologic Markers in Crohn’s Disease

New serologic markers of inflammatory bowel disease may be useful for differentiating between Crohn's disease and ulcerative colitis and for disease stratification. We profiled sugar-binding antibodies to identify novel antiglycan antibodies that may be associated with inflammatory bowel disease. Serum samples were obtained from patients with diagnosed Crohn's disease or ulcerative colitis and from control patients. The presence of antiglycan antibodies was evaluated using either a glycan array (GlycoChip; Glycominds, Ltd, Lod, Israel) in patients with Crohn's disease (n = 72) or ulcerative colitis (n = 56) and in healthy controls (n = 41) or using an enzyme-linked immunosorbent assay in patients with Crohn's disease (n = 124), ulcerative colitis (n = 106), and in control patients (n = 101). Inaddition to antibodies against mannan, antibodies to laminaribioside (Glc[beta1,3]Glc[beta]) and chitobioside (GlcNAc[beta1,4]GlcNAc[beta]) had the highest discriminative capability between Crohn's disease and ulcerative colitis (P < .001 and P < .05, respectively). Importantly, 44% (12/27) of anti-Saccharomyces cerevisiae antibody-negative Crohn's disease patients were positive for antilaminaribioside or antichitobioside. In patients with inflammatory bowel disease positive for antibodies against either laminaribioside, chitobioside, or mannan, the diagnosis of Crohn's disease was suggested with a sensitivity of 77.4% and specificity of 90.6%. Having at least 2 of these antibodies increased the specificity to 99.1%. In Crohn's disease, higher levels of antibodies against laminaribioside or mannan were significantly associated with small intestinal disease (P = .03 and P < .0001, respectively). Antilaminaribioside and antichitobioside carbohydrate antibodies are novel serologic markers associated with Crohn's disease. These antibodies may contribute to the diagnosis and improved stratification of Crohn's disease.