Anti-saccharomyces cerevisiae antibodies (ASCA) in coeliac disease

Alessandro Granito, MD,

Other Contributors:

August 25, 2005

Dear Editor,

We read with great interest the paper by Israeli et al. assessing the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) before the occurrence of overt clinical manifestations in patients with Crohn’s disease (CD) and ulcerative colitis (UC).[1] They found that ASCA were present in 31% CD patients before clinical diagnosis (but not in UC patients and controls), and that pANCA were detectable in 2 (25%) of 8 UC patients before clinical manifestations, but not in 24 matched controls. This observation led the Authors to conclude that ASCA and pANCA may predict the development of inflammatory bowel disease long before its clinical onset.

We have recently published our experience on the prevalence and behaviour of ASCA and pANCA in adult and paediatric coeliac disease patients.[2] Sixty-two (59%) of 105 coeliac patients had IgA and/or IgG ASCA (Quanta Lite ASCA IgG and IgA assay, Inova Diagnostics, San Diego, CA, USA) at diagnosis, while only one patient (0.9%) had pANCA. No significant correlation was found between ASCA positivity and severity of small intestinal mucosal damage. Moreover, after gluten free diet (mean 14.4 months 2.7) 93% of the revaluated coeliac patients lost IgA ASCA, whereas 83% maintained the IgG ASCA reactivity.

Interestingly, 7 coeliac patients (6 woman, median age 26, range 18-33) of the 62 with IgA and/or IgG ASCA were diagnosed before developing any clinical symptom, since they were screened as first degree relatives of coeliac patients. All of them had anti-tissue transglutaminase antibodies (tTG), anti-endomysial antibodies (EmA), the HLA DQ2/DQ8 haplotype, and a histological picture on small intestinal biopsy showing an increased number of intraepithelial lymphocytes in 5, and mild villous flattening in 2 (grade 1 and grade 3a respectively, according to Marsh’s classification modified by Oberhuber).

In this type of patients, known as having respectively a “potential” and “silent” coeliac disease, the positivity of serological markers (EmA and tTG) together with typical HLA predisposing genotype (DQ2 or DQ8), allows to make accidentally a diagnosis of gluten enteropathy also when clinical manifestation is still lacking.[3,4]

Our observation indicates that in asymptomatic patients ASCA positivity not only is predictive of CD, but also may be associated to “potential/silent” coeliac disease. The increased permeability in the small bowel of coeliac patients seems to be an early event, preceding the development of a more severe mucosal damage.[5,6]

Similarly to asymptomatic CD patients, also in asymptomatic coeliac patients the altered permeability of the small bowel toward yeast antigens could account for the occurrence of ASCA since the very early stage of the disease as suggested by our 5 coeliac patients with minimally abnormal mucosal architecture. The “altered permeability” hypothesis should be investigated further to explain the frequent detection of ASCA also in autoimmune disorders such as primary biliary cirrhosis and primary sclerosing cholangitis.[7]


1. Israeli E, Grotto I, Gilburd B, et al. Anti-Saccharomyces cerevisiae and neutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut 2005;54:1232-1236.

2. Granito A, Zauli D, Muratori P, et al. Anti-Saccharomyces cerevisiae and neutrophil cytoplasmic antibodies in coeliac disease before and after gluten free diet. Aliment Pharmacol Ther 2005;21:881-887.

3. Fasano A, Catassi C. Current approaches to diagnosis and treatment of coeliac disease: an evolving spectrum. Gastroenerology 2001;120:636-651.

4. Vasquez H, Cabanne A, Sugai E, et al. Serological markers identify histologically latent coeliac disease among first-degree relatives. Eur J Gastroenterol Hepatol 1996;8:15-21.

5. van Elburg RM, Uil JJ, Mulder CJ, et al. Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease. Gut 1993;34:354-357.

6. Clemente MG, De Virgiliis S, Kang JS, et al. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut 2003;52:218-223.

7. Muratori P, Muratori L, Guidi M, et al. Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases. Clin Exp Immunol 2003;132:473-6.

Conflict of Interest

None declared