We read with great interest the paper by Israeli and colleagues (Gut 2005;54:1232–6) 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). They found that ASCA were present in 31% of CD patients before clinical diagnosis (but not in UC patients or controls), and that pANCA were detectable in two (25%) of eight UC patients before clinical manifestations but not in 24 matched controls. These observations 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.1 Sixty two (59%) of 105 coeliac patients had IgA and/or IgG ASCA (Quanta Lite ASCA IgG and IgA assay; Inova Diagnostics, San Diego, California, 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 a gluten free diet (mean 14.4 (2.7) months), 93% of revaluated coeliac patients lost IgA ASCA whereas 83% maintained IgG ASCA reactivity.
Interestingly, seven (six women; median age 26 (range 18–33) years) of the 62 coeliac patients with IgA and/or IgG ASCA were diagnosed before developing any clinical symptoms as they were screened as first degree relatives of coeliac patients. All had antitissue transglutaminase antibodies (tTG), antiendomysial antibodies (EmA), the HLA DQ2/DQ8 haplotype, and a histological picture on small intestinal biopsy showing an increased number of intraepithelial lymphocytes in five and mild villous flattening in two (grade 1 and grade 3a, respectively, according to Marsh's classification modified by Oberhuber).
In this type of patient, known as having “potential” and “silent” coeliac disease, respectively, positivity for the serological markers (EmA and tTG) together with the typical HLA predisposing genotype (DQ2 or DQ8) allows accidental diagnosis of gluten enteropathy when clinical manifestations are still lacking.2,3
Our observation indicates that in asymptomatic patients, ASCA positivity is not only predictive of CD but may also be associated with “potential/silent” coeliac disease. Increased permeability in the small bowel of coeliac patients seems to be an early event, preceding the development of more severe mucosal damage.4,5 Similar to asymptomatic CD patients, the altered permeability of the small bowel towards yeast antigens could account for the occurrence of ASCA from a very early stage of the disease in asymptomatic coeliac patients, as suggested by our five coeliac patients with minimally abnormal mucosal architecture. The “altered permeability” hypothesis should be investigated further to explain the frequent detection of ASCA in other autoimmune disorders, such as primary biliary cirrhosis and primary sclerosing cholangitis.6
Footnotes
Conflict of interest: None declared.
References
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