anti-Saccharomyces Cerevisiae Mannan Antibodies Research Articles

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.

Serological markers predict inflammatory bowel disease years before the diagnosis

ObjectiveAnti-neutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) have been detected in the serum of patients with ulcerative colitis (UC) and Crohn's disease (CD) and their unaffected family members....

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.

Elevated Levels of Serum IgA Against Saccharomyces Cerevisiae Mannan in Patients with Rheumatoid Arthritis

This study was undertaken to investigate whether levels of anti-Saccharomyces cerevisiae mannan antibodies (ASCMA) in human sera, a marker for several autoimmune diseases, correlate with rheumatoid arthritis (RA). ASCMA-IgA, -IgG and -IgM levels were measured with enzyme linked immunosorbent assays (ELISA) in patients with RA (n = 30) and 152 healthy adult controls. ASCMA-IgA prevalence was significantly higher in RA patients (40%) than in healthy subjects (5.3%). A strong correlation between levels of ASCMA-IgA and CRP (r = 0.695; p < 0.01) and ESR (r = 0.708; p < 0.01) in RA patients was observed. No significant differences in ASCMA-IgG or IgM levels were noted between RA patients and healthy control subjects in the present study. This result differs from previous reports. It remains to be evaluated whether elevated ASCMA-levels are common to all rheumatic disorders.

Elevated levels of serum antibodies against Saccharomyces cerevisiae mannan in patients with systemic lupus erythematosus

This study was undertaken to investigate whether levels of anti-Saccharomyces cerevisiae mannan antibodies (ASCMAs), a serological marker for Crohn's disease, seronegative spondyloarthritis and Behcet's disease, also correlate with systemic lupus erythematosus (SLE) in humans. Serum samples from healthy volunteers (n = 152) and patients with SLE (n = 40) were compared for ASCMA-IgA, -IgG and -IgM levels using enzyme linked immunosorbent assays. ASCMA-IgG, but not IgM and IgA, prevalence was significantly raised in active SLE patients (57.5%) compared with healthy controls (8.5%). ASCMA-IgG levels in SLE patients during remission were relatively lower, indicating a possible correlation with disease activity. These results differ from a previous study, which did not detect a difference between ASCMA levels in SLE patients and healthy control. It remains to be evaluated whether elevated ASCMA-levels are common to all rheumatic disorders.

Recurrent Autoimmune Pancreatitis in a 10‐Year‐Old Boy

Recurrent Autoimmune Pancreatitis in a 10‐Year‐Old Boy

Pathogenic agents in inflammatory bowel diseases

Infectious agents are still thought to be involved in the origin of inflammatory bowel disease. The focus in recent years has been more on Mycobacterium avium subsp paratuberculosis, adherent-invasive Escherichia coli or yeasts. A metaanalysis has shown a significant association of M. avium subsp paratuberculosis and Crohn's disease and a large randomized placebo-controlled trial reported an absence of sustained beneficial effects of combined antibiotic therapy on remission of active Crohn's disease. Adherent-invasive E. coli adhere via type 1 pili to carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), abnormally expressed by intestinal epithelial cells in Crohn's disease patients. Both colonization of the ileal mucosa and stimulation of ileal epithelial cells by tumour necrosis factor-alpha induce overexpression of CEACAM6, leading to an amplification loop of colonization and inflammation. Anti-Saccharomyces cerevisiae mannan antibodies are the most prevalent serologic marker in Crohn's disease. Major oligomannose epitopes supporting antibody formation are expressed by Candida albicans in human tissues, suggesting that a loss of tolerance to C. albicans could lead to antibody formation in a subset of Crohn's disease patients who are genetically predisposed. M. avium subsp paratuberculosis, adherent-invasive E. coli and Candida are good candidates for an infectious aetiology of Crohn's disease on the basis of genetic susceptibility, which relates to impaired function in the defence against intracellular bacteria.

Anti-Saccharomyces cerevisiae mannan antibodies (ASCA) of Crohnʼs patients crossreact with mannan from other yeast strains, and murine ASCA IgM can be experimentally induced with Candida albicans

Anti-Saccharomyces cerevisiae antibodies (ASCA) present in a subgroup of Crohn's disease (CD) patients indicate loss of tolerance against commensal antigens. ASCA can be induced in Candida albicans-infected rabbits, suggesting their potential crossreactive nature. The present study aimed to determine crossreactivities of ASCA with cell wall mannans from other yeasts, including the opportunistic pathogen C. albicans, and to define the requirements for (crossreactive) ASCA in experimental mice. ASCA were determined by enzyme-linked immunosorbent assay (ELISA). ASCA were neutralized by preincubating sera with purified mannans. Binding of ASCA was visualized by Western blot. Mice were immunized with live yeasts and experimental colitis was induced with dextran sodium sulfate (DSS). Seroreactivity of ASCA-positive CD patients against S. cerevisiae mannan significantly correlates with that against mannans from 5 other yeast species, including C. albicans. This correlation is due to crossreactive IgG, demonstrated by the loss of reactivity after preincubation of sera with mannans from the other yeasts. Immunization of mice with S. cerevisiae or C. albicans fails to induce (crossreactive) ASCA IgM or IgG antibodies. Subsequent chronic experimental colitis concomitant with feeding live yeasts promotes ASCA IgM but not IgG generation, while titers remain modest compared to those in ASCA-positive CD patients. Correlations of ASCA reactivities against mannans from different yeasts are due to crossreactive IgGs. The inability of mice to readily generate ASCA is in line with the current opinion that genetic predisposition is a prerequisite for the development of this and other unusual immune reactivities in CD.

Relevance of serologic studies in inflammatory bowel disease

The serologic panel for inflammatory bowel disease (IBD) is rapidly expanding. Antineutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae mannan antibodies (ASCA) have remained the most widely studied markers, but immune reactivity against a new group of bacterial antigens such as I2, OmpC (outer membrane porin C), and flagellin, has been described in Crohn's disease. Several clinical avenues have been explored, such as the usefulness of serologic markers as screening tools for IBD and in accelerating a diagnosis in patients with indeterminate colitis. Another area of interest is disease stratification. Emerging data suggest there is a diversity of qualitative and quantitative responses to environmental antigens that differs among groups of IBD patients and may be associated with different clinical behaviors. As a result, it may be possible to tailor therapy on the basis of serologic responses. Prospective studies are needed before translating this concept into clinical practice. Clustering of IBD patients into more homogeneous subgroups based on antibody responses may help to unravel the pathophysiology of subsets of IBD.

Serological markers in inflammatory bowel diseases

This chapter is an overview of the literature on serological markers of inflammatory bowel diseases (IBD), focusing on anti-neutrophil cytoplasm autoantibodies (ANCA) and anti- Saccharomyces cerevisiae mannan antibodies (ASCA). The methodology for ANCA and ASCA testing is first introduced. The value of these markers as diagnostic tools is then discussed. Other chapters are devoted to the potential role of ANCA and ASCA in disease monitoring, disease stratification and as subclinical markers in families. Finally reviewed are other antibodies recently tested in clinical trials such as pancreatic antibodies and antibodies directed against bacterial antigens. The role of these antibodies in the pathophysiology of IBD still needs to be assessed. We also need to identify the ASCA immunogen(s) eliciting the antibody response.

Diagnostic role of anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic antibodies in patients with inflammatory bowel disease.

Perinuclear antineutrophil cytoplasmic autoantibody is known to be a marker for ulcerative colitis, and anti-Saccharomyces cerevisiae Mannan antibody is a serologic marker associated with Crohn's disease. The aim of this study was to assess the value of detecting perinuclear antineutrophil cytoplasmic autoantibody and/or anti-Saccharomyces cerevisiae Mannan antibody for the diagnosis of ulcerative colitis, Crohn's disease, Behçet's colitis, and tuberculous colitis. Serum samples were obtained from 85 patients with Crohn's disease, 77 with ulcerative colitis, 36 with Behçet's colitis, 14 with tuberculous colitis, 20 healthy controls, and 21 first-degree relatives of patients with Crohn's disease. Determination of perinuclear antineutrophil cytoplasmic autoantibody and anti-Saccharomyces cerevisiae Mannan antibody was performed with the standardized indirect immunofluorescence technique and an enzyme-linked immunosorbent assay, respectively. A relatively high percentage of patients with Crohn's disease (49.4 percent), relatives of Crohn's disease patients (61.9 percent), and patients with Behçet's disease (41.7 percent) tested seropositive for anti-Saccharomyces cerevisiae Mannan antibody compared with normal controls (10 percent). In cases of ulcerative colitis, 44.2 percent tested seropositive for perinuclear antineutrophil cytoplasmic autoantibody, whereas the controls showed 0 percent positivity. The combination of a positive anti-Saccharomyces cerevisiae Mannan antibody test and a negative perinuclear antineutrophil cytoplasmic autoantibody yielded a sensitivity and specificity of 48.2 and 87 percent, respectively, for Crohn's disease. The combination of a positive perinuclear antineutrophil cytoplasmic autoantibody test and a negative anti-Saccharomyces cerevisiae Mannan antibody test yielded a sensitivity and specificity of 36.4 and 97.6 percent, respectively, for ulcerative colitis. Anti-Saccharomyces cerevisiae Mannan antibody may be associated with Crohn's disease and Behçet's disease and perinuclear antineutrophil cytoplasmic autoantibody with ulcerative colitis. A combination of both tests may aid the differential diagnosis of inflammatory bowel disease.

Serological markers in inflammatory bowel disease: the pros and cons.

Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease. Among several serological markers anti-Saccharomyces cerevisiae mannan antibodies and perinuclear antineutrophil cytoplasmic autoantibodies are highly disease specific for Crohn's disease and ulcerative colitis, respectively. Combining the two improves their specificity. Sensitivity, however, is still low. Due to lack of standardization and vast interobserver variability, they cannot be used as the only diagnostic criteria but can assist clinicians in diagnosing and categorizing patients with inflammatory bowel disease as well as in helping them to take therapeutic decisions.

Anti-saccharomyces cerevisiae mannan antibodies: Are they useful in clinical practice?

Anti-saccharomyces cerevisiae mannan antibodies: Are they useful in clinical practice?

Anti-saccharomyces cerevisiae mannan antibodies: Are they useful in clinical practice?

Anti-saccharomyces cerevisiae mannan antibodies: Are they useful in clinical practice?

Familial expression of anti- Saccharomyces cerevisiae mannan antibodies in Crohn’s disease and ulcerative colitis: a GISC study

OBJECTIVES: Recent studies in familial Crohn’s disease (CD) have suggested that anti- Saccharomyces cerevisiae mannan antibodies (ASCAs) may represent a new specific marker of genetic susceptibility. In this study we aimed to assess the importance of ASCAs by comparing their presence in a large number of patients with sporadic and familial occurrence of CD or ulcerative colitis (UC) and their unaffected relatives. METHODS: Serum samples from 96 patients with sporadic CD, 97 patients with sporadic UC, and 50 unrelated healthy controls were tested for ASCAs by a standard ELISA method. Moreover, 73 families with two or more members affected by CD and/or UC were recruited. From these families 58 CD patients, 84 UC patients, and 216 unaffected first degree relatives were investigated. RESULTS: ASCAs were detected in 34 of 96 patients with sporadic CD (35%, p < 0.01 vs controls), 11 of 97 patients with sporadic UC (12%), and two of 50 controls (4%). ASCAs were significantly ( p < 0.04) more frequent in patients with familial CD (55%) and familial UC (25%) than in sporadic cases. Moreover, ASCAs were found in 25% of unaffected relatives, and this rate did not significantly differ in CD, UC, and mixed families (28%, 26%, and 22%, respectively). CONCLUSIONS: In this study we confirm that ASCAs occur particularly frequently in CD patients, especially with the presence of a positive family history. However, they are also significantly increased in UC patients with a family history and in a considerable number of unaffected relatives of inflammatory bowel disease families, irrespective of the characteristics of their families (UC, CD, mixed, ASCA positive, and ASCA negative). The presence of ASCAs in unaffected relatives might point toward a genetic predisposition to either CD or UC.

Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study.

Recent studies in familial Crohn's disease (CD) have suggested that anti-Saccharomyces cerevisiae mannan antibodies (ASCAs) may represent a new specific marker of genetic susceptibility. In this study we aimed to assess the importance of ASCAs by comparing their presence in a large number of patients with sporadic and familial occurrence of CD or ulcerative colitis (UC) and their unaffected relatives. Serum samples from 96 patients with sporadic CD, 97 patients with sporadic UC, and 50 unrelated healthy controls were tested for ASCAs by a standard ELISA method. Moreover, 73 families with two or more members affected by CD and/or UC were recruited. From these families 58 CD patients, 84 UC patients, and 216 unaffected first degree relatives were investigated. ASCAs were detected in 34 of 96 patients with sporadic CD (35%, p < 0.01 vs controls), 11 of 97 patients with sporadic UC (12%), and two of 50 controls (4%). ASCAs were significantly (p < 0.04) more frequent in patients with familial CD (55%) and familial UC (25%) than in sporadic cases. Moreover, ASCAs were found in 25% of unaffected relatives, and this rate did not significantly differ in CD, UC, and mixed families (28%, 26%, and 22%, respectively). In this study we confirm that ASCAs occur particularly frequently in CD patients, especially with the presence of a positive family history. However, they are also significantly increased in UC patients with a family history and in a considerable number of unaffected relatives of inflammatory bowel disease families, irrespective of the characteristics of their families (UC, CD, mixed, ASCA positive, and ASCA negative). The presence of ASCAs in unaffected relatives might point toward a genetic predisposition to either CD or UC.

Anti– saccharomyces cerevisiae mannan antibodies and antineutrophil cytoplasmic autoantibodies in Greek patients with inflammatory bowel disease

OBJECTIVES: The combined measurement of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti– Saccharomyces cerevisiae mannan antibodies (ASCA) has recently been suggested as a valuable diagnostic approach in inflammatory bowel disease (IBD). The aim of this study was to assess the value of detecting pANCA and ASCA in the differentiation between ulcerative colitis (UC) and Crohn’s disease (CD) in a Greek population with IBD. METHODS: Sera were collected from 157 patients with IBD (97 with UC, 56 with CD, and four with indeterminate colitis) and 150 healthy controls. Determination of pANCA was performed by a standard indirect immunofluorescence technique on ethanol-fixed granulocytes and ASCA by an ELISA assay. RESULTS: In patients with UC, sensitivity, specificity, positive predictive value, and negative predictive value of the pANCA test was 67%, 84%, 93%, and 46% respectively. These values did not change significantly when the combination of positive pANCA and negative ASCA was used. ASCA test in diagnosing CD yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 54%, and 81%. The combination of pANCA negative and ASCA positive increased the positive predictive value to 77% and it was associated with small bowel disease. CONCLUSIONS: A positive pANCA test in Greek patients has a diagnostic value in confirming a diagnosis of UC. Measurement of pANCA and ASCA together has a rather limited value in the differential diagnosis between UC and CD but may be of help in studying disease heterogeneity.

Anti-Saccharomyces cerevisiae mannan antibodies and antineutrophil cytoplasmic autoantibodies in Greek patients with inflammatory bowel disease.

The combined measurement of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) and anti-Saccharomyces cerevisiae mannan antibodies (ASCA) has recently been suggested as a valuable diagnostic approach in inflammatory bowel disease (IBD). The aim of this study was to assess the value of detecting pANCA and ASCA in the differentiation between ulcerative colitis (UC) and Crohn's disease (CD) in a Greek population with IBD. Sera were collected from 157 patients with IBD (97 with UC, 56 with CD, and four with indeterminate colitis) and 150 healthy controls. Determination of pANCA was performed by a standard indirect immunofluorescence technique on ethanol-fixed granulocytes and ASCA by an ELISA assay. In patients with UC, sensitivity, specificity, positive predictive value, and negative predictive value of the pANCA test was 67%, 84%, 93%, and 46% respectively. These values did not change significantly when the combination of positive pANCA and negative ASCA was used. ASCA test in diagnosing CD yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 39%, 89%, 54%, and 81%. The combination of pANCA negative and ASCA positive increased the positive predictive value to 77% and it was associated with small bowel disease. A positive pANCA test in Greek patients has a diagnostic value in confirming a diagnosis of UC. Measurement of pANCA and ASCA together has a rather limited value in the differential diagnosis between UC and CD but may be of help in studying disease heterogeneity.

Familial expression of anti-Saccharomyces cerevisiae mannan antibodies in affected and unaffected relatives of patients with Crohn's disease

BACKGROUNDCrohn's disease is a familial disorder, and antiglycan antibodies to the cell wall mannan ofSaccharomyces cerevisiae (ASCA) are highly correlated with Crohn's disease.AIMSTo determine whether there is a familial pattern...

Anti- Saccharomyces cerevisiae mannan antibodies in familial crohn’s disease

Objective: Anti- Saccharomyces cerevisiae mannan antibodies (ASCA) are associated with Crohn’s disease. The aim of this study was to determine the prevalence of ASCA in families in which at least two members were affected with Crohn’s disease. Methods: A total of 20 families including two (n = 15) or more (n = 5) patients with Crohn’s disease were tested for ASCA with use of an ELISA method. Overall, 51 affected members, 66 healthy first degree relatives, and 163 healthy control subjects were studied. Results: ASCA were detected in 35 of 51 (69%) patients with Crohn’s disease and in 13 of 66 (20%) healthy relatives versus one of 163 healthy control subjects ( p < 0.0001 and p < 0.001). ASCA-positive relatives were distributed in 12 of 20 families. ASCA were present in eight healthy parents and four healthy siblings. The prevalence of ASCA in relatives did not depend on the ASCA status of affected members. Conclusion: ASCA in 20% of healthy first degree relatives of patients with Crohn’s disease suggest that these antibodies might be a subclinical marker for Crohn’s disease in families. Whether ASCA reflect environmental or genetic factors or a combination of both is unknown.