Are serological tests for IBD useful to clinicians?

Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role. Quinton JF, Sendid B, Reumaux D, Duthilleul P, Cortot A, Grandbastien B, Charrier G, Targan SR, Colombel JF, Poulain D. Gut 1998;42:788-91. Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) have become established as a marker of ulcerative colitis (UC). More recently, antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) have been the focus of much interest as a marker of Crohn's disease (CD). The authors assessed the diagnostic value of detecting pANCA and/or ASCA for the diagnosis of UC and CD. The study population consisted of 100 adult patients with CD, 101 with UC, 27 with various other diarrheal disorders, and 163 healthy controls. The combination of a positive pANCA and negative ASCA tests yielded a sensitivity, specificity, and positive predictive values of 57, 97 and 92.5%, respectively, for UC. The combination of a positive ASCA and negative pANCA tests yielded 49, 97, and 92.5% for the same parameters. Using multivariate analysis, ASCA in CD was found to be associated with small bowel involvement. The authors concluded that ASCA and pANCA are strongly associated with CD and UC, respectively. Comment: The article by Quinton et al. raises the question as to the clinical usefulness and role for serological tests in IBD. Most clinicians would argue that they are certainly capable of diagnosing IBD using the gold standard combination of radiological, endoscopic, and histologic criteria. What then is the place for these antibody assays? There is no doubt that in many cases, especially those that are the most severely affected, an experienced clinician can make a diagnosis of IBD on the basis of the history and physical examination alone. In such instances, we carry out colonoscopies and barium studies to provide histological confirmation and for determining the extent of involvement. Do experienced clinicians need serological assays in their diagnostic armamentarium? In my opinion, I would say yes. The answer to my rhetorical question is based on the diagnostic accuracy of the tests in question. In UC, pANCA have been reported to be present in 40-80% of cases, with a high degree of disease specificity (Gastroenterology 1991;100: 1590-6; Gastroenterology 1998;115:822-9). Similarly, ASCA has been reported to be 64% sensitive and 77% specific for discriminating CD from UC and 89% specific for distinguishing CD from controls (Clin Diag Lab Immunol 1996;3:219-26). The results of the present study thus confirm previous reports. A recent study found similar results for the diagnostic accuracy of ASCA and pANCA in pediatric IBD patients (Gastroenterology 1998;115:822-9). In the present and the pediatric study, the sensitivity of ASCA in patients with CD restricted to the colon was 45 and 47%, respectively. However, in the latter study, “double ASCA positivity” (IgG and IgA titers) was 100% specific for CD (Gastroenterology 1998;115:822-9). In the above study by Quinton and colleagues, it is not clear whether ASCA positivity related to IgG only, or to other isotypes as well. These findings have important clinical implications with respect to differentiating CD from UC in patients with colitis, or for cases of “indeterminate colitis.” CD patients with a “UC-like” presentation are often pANCA positive (Gastroenterology 1996;110:1810-9). Therefore, only the presence of ASCA can truly be considered specific for CD. In the above study by Quinton et al., pANCA negative/ASCA positive results were 97% specific and had a 96% positive predictive value for CD, whereas pANCA positive/ASCA negative assays were 97% specific and 92.5% predictive value positive for UC. In view of the disparate prognosis after colectomy in UC vs. CD, the data thus suggest that ASCA and pANCA testing should be carried out prior to elective “curative” surgery for UC. In many cases, the diagnosis of IBD is delayed due to nonspecific presenting complaints. Reliable screening tests would be potentially helpful in these circumstances, allowing the clinician to expedite the diagnosis. Furthermore, a high negative predictive value of serological tests would potentially avoid unnecessary, more-invasive and costly testing. In the study by Quinton et al. the negative predictive value of ASCA for CD was 94.5%. However, it is not at all clear that the study was carried out prospectively. Nor did all patients have symptoms potentially consistent with IBD. On the contrary, all but 27 of the 190 non-IBD control patients were healthy individuals who had no gastrointestinal symptoms or family history of IBD. Furthermore, the clinical value of any test is overestimated when the prevalence of the disease in the population studied is artificially high, such as in the above report (201 of 391 patients studied had IBD). Further prospective studies using ASCA thus need to be carried out in patients with gastrointestinal complaints so that the true diagnostic accuracy of this very promising test can be established.

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