Update in Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: Results of a multicenter study

Laboratoire d'Immunologie, CHU de la Conception, 147, Bd Baille, Marseille 13005, France.
World Journal of Gastroenterology (Impact Factor: 2.37). 05/2007; 13(16):2312-8.
Source: PubMed


Anti-Saccharomyces cerevisiae antibodies (ASCA), anti-nuclear associated anti-neutrophil antibodies (NANA) and antibodies to exocrine pancreas (PAB), are serological tools for discriminating Crohn's disease (CrD) and ulcerative colitis (UC). Like CrD, coeliac disease (CoD) is an inflammatory bowel disease (IBD) associated with (auto) antibodies. Performing a multicenter study we primarily aimed to determine the performance of ASCA, NANA and PAB tests for IBD diagnosis in children and adults, and secondarily to evaluate the prevalence of these markers in CoD.
Sera of 109 patients with CrD, 78 with UC, 45 with CoD and 50 healthy blood donors were retrospectively included. ASCA, NANA and PAB were detected by indirect immunofluorescence (IIF).
ASCA+/NANA- profile displayed a positive predictive value of 94.2% for CrD. Detection of ASCA was correlated with a more severe clinical profile of CrD and treatment of the disease did not influence their serum levels. ASCA positivity was found in 37.9% of active CoD. PAB were found in 36.7% CrD and 13.3% CoD patients and were not correlated with clinical features of CrD, except with an early onset of the disease. Fifteen CrD patients were ASCA negative and PAB positive.
ASCA and PAB detected by IIF are specific markers for CrD although their presence does not rule out a possible active CoD. The combination of ASCA, NANA and PAB tests improves the sensitivity of immunological markers for CrD. Repeating ASCA, NANA, and PAB testing during the course of CrD has no clinical value.

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    • "Two recent meta-analyses [6] [9] indicated that positive ASCA serum status is associated with early-onset age, ileal involvement, complicated behavior, perianal disease and requirement for surgery in CD. In a previous study [25] we agreed with some of these data but in the present study we highlighted the specificities of a CD patient cohort with isolated colonic involvement and no pediatric case have been included. For this particular cohort of CD, to our knowledge, literature data are now lacking. "
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    ABSTRACT: Antibodies against Saccharomyces cerevisiae (ASCA) and Escherichia coli outer membrane porin C (anti-OmpC) are known to be detectable in the serum of patients with Crohn’s disease (CD) but display a very poor sensitivity for the disease especially in forms with isolated colonic involvement. In this study we aimed at evaluating performances of these markers in supernatant of cultured colonic biopsies. Patients with colonic CD (n = 67), ulcerative colitis (UC) (n = 35) and control individuals (n = 37) were prospectively recruited for colonoscopy pinch biopsies and blood sampling. Serum and supernatant of culture tissues were analyzed for ASCA and anti-OmpC. Direct immunofluorescence was also performed on colonic tissues for total IgA detection. We detected for the first time ASCA IgA/IgG and anti-OmpC IgA in cultured colonic tissue supernatants. For both markers, sensitivities for diagnosing CD were better in supernatants (ASCA: 53.7%, anti-OmpC: 28.4%) than in serum (ASCA: 31.3%, anti-OmpC: 22.4%). Combination of results from a panel of these tests gave the greatest sensitivity ever described for CD diagnosis in colonic forms (70.2%). In this study, we described, for the first time, ASCA in supernatant of colonic tissue cultures. This assaying approach in CD diagnosis should be taken into consideration in the future especially in CD forms with isolated colonic involvement.
    Full-text · Article · Nov 2013 · PLoS ONE
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    • "Traditionally, the combination of a positive anti-Saccharomyces cerevisiae antibodies (ASCA) test with a negative perinuclear antineutrophil cytoplasmic antibodies (pANCA) test has been utilized as serological markers for discriminating cases of CD colitis from UC [37], [38]. However, there are concerns regarding the utility of these tests, because data show that almost half of the patients may not develop ASCA or pANCA antibodies [39]–[41]. In fact, many studies have shown that patients with diseases other than CD, for example, Behcet disease, ankylosing spondylitis and cystic fibrosis, may also have a higher frequency of ASCA seropositivity than the general population [42]–[44]. "
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    ABSTRACT: In about 10-15% of patients with inflammatory bowel diseases (IBD) there is no clear definitive differential diagnosis between Crohn's disease (CD) and ulcerative colitis (UC) and the disease is classified as indeterminate colitis. Since pharmacological and surgical treatments differ in CD and UC, establishing a correct diagnosis is critical. The aim of this work was to access the expression profile of proteins involved in colonic inflammation and cancer in samples from CD and UC. For that, colon samples from 24 CD, 21 UC and 10 control patients were processed for immunohistochemistry using anti-phosphorylated RB at Ser(807/811) and anti-β-catenin. Crypts were blinded, analyzed and counted for phosphorylated RB-positive (phospho-RB) cells or scored for positive β-catenin staining. Western blot was used for confirming immuhistochemical results: RB phosphorylation was significantly greater in colon samples from patients with CD compared with UC (p<0.005). In contrast, the expression of β-catenin was significantly increased in UC compared with CD (p<0.005) samples. Phospho-RB and β-catenin are negatively correlated (CC: -0.573; p = 0.001). A positive phospho-RB test yielded high levels of sensitivity, specificity, negative and positive predictive values, and accuracy for the diagnosis of CD against UC. This work indicates that RB phosphorylation and β-catenin nuclear translocation are differently expressed in CD and UC, and provide novel insights into the pathogenic mechanisms of IBD. In particular, rates of phospho-RB-positive cells in mucosal samples emerge as a promising tool for the differential diagnosis of patients with IBD.
    Full-text · Article · Aug 2013 · PLoS ONE
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    • "Another issue investigated in PAB studies is the relationship between PAB and concomitant drugs. Despite the studies by Stöcker et al [9] and Folwaczny et al [10] that have reported a high antibody frequency in patients not using glucocorticosteroids, Seibold et al [7,21] , Goischke et al [12] and Klebl et al [16] did not detect any relationship between PAB frequency and drug use, including glucocorticosteroids . In our study, PAB positivity rates showed no difference between CD patients who were and were not taking glucocorticosteroids. Similarly, no statistically significant difference was noted in patients who were and were not using AZA. "

    Preview · Article · Jan 2010 · World Journal of Gastroenterology
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