Letters to the Editor
Association between intestinal permeability and anti-Saccharomyces cerevisiae antibodies in patients with Crohn's disease
Article first published online: 1 MAY 2008
Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 14, Issue 11, pages 1610–1611, November 2008
How to Cite
Benjamin, J., Makharia, G. K. and Joshi, Y. K. (2008), Association between intestinal permeability and anti-Saccharomyces cerevisiae antibodies in patients with Crohn's disease. Inflamm Bowel Dis, 14: 1610–1611. doi: 10.1002/ibd.20479
- Issue published online: 15 OCT 2008
- Article first published online: 1 MAY 2008
To the Editor:
A nti-Saccharomyces cerevisiae antibodies (ASCA) are positive in 60%–80% of patients with Crohn's disease (CD).1, 2 ASCA has been used for the differentiation of ulcerative colitis (UC) from CD. The postulations of ASCA positivity in patients with CD include genetic predisposition, crossreactivity, and increased intestinal permeability, although the exact mechanism is not yet known. Forty to 60% of patients with CD also have an increase in intestinal permeability.3 Hence, it is intriguing to know whether ASCA positivity is an epiphenomenon or a manifestation of increased intestinal permeability in patients with CD.
Of 125 patients with CD with results of intestinal permeability, we retrieved the records of 50 patients from whom sera were also available within 3 months of collection of urine for estimation of ASCA antibodies. The diagnosis of CD was made on ECCO guidelines.4 Disease activity was assessed using the Crohn's Disease Activity Index (CDAI) and the location and behavior of the disease were classified using the modified Montreal classification. All the patients were treated according to standard guidelines.
Intestinal permeability was measured by lactulose mannitol (LM ratio) excretion in urine over 5 hours after oral ingestion of 5 g of lactulose and 2 g of mannitol. Based on the LM ratio of 22 healthy controls, the upper limit of normal for the LM ratio in our laboratory is 0.0373. All the patients and healthy subjects were instructed to abstain from nonsteroidal antiinflammatory drugs (NSAIDs) for 2 weeks prior to the test.
A standard enzyme-linked immunosorbent assay (ELISA) was employed for qualitative detection of ASCA IgA and ASCA IgG in the serum using commercially available kits from AESKU Diagnostics (Germany). A positive and negative control along with a “cutoff” was run with each group of samples and the procedure was performed according to the instructions of the manufacturer. The cutoff value for a positive test for ASCA IgA and IgG were 15 U and 20 U, respectively.
STATA 9.0 (College Station, TX) statistical software was used for data analysis. The association between IP (LMR) and ASCA (IgG, IgA) was assessed using Spearman's correlation. The prevalence of the positivity of ASCA IgG and IgA in patients with abnormal and normal intestinal permeability was compared using chi-square tests.
Intestinal permeability was increased (LM ratio >0.0373) in 20/50 (40%) of the patients with CD. The data for ASCA IgA and ASCA IgG are shown in Table 1. No significant correlation was found between intestinal permeability (LM ratio) and ASCA IgA (r = 0.151, P = 0.294) and ASCA IgG (r = 0.140, P = 0.331). Similarly, no association was seen between ASCA positivity and increased intestinal permeability.
|Only IgA +||19 (38%)|
|Only IgG +||13 (26%)|
|Either IgG or IgA +||22 (44%)|
|Both IgG & IgA +||10 (20%)|
Saccharomyces cerevisiae is a “ubiquitous” yeast and is present naturally on plants and in the soil.5 Humans are exposed to this yeast principally by food products and beverages. It is generally accepted that S. cerevisiae is not a pathogen, but in an immunocompromised host, fungemia with S. cerevisiae can prove to be pathogenic.5 The most popular hypothesis of a positive ASCA is postulated to be increased intestinal permeability that might lead to increased exposure of yeast antigens to immune reactive cells.6, 7 However, in this study we did not find any association between abnormal intestinal permeability and ASCA positivity, as also reported by Harrer et al.8 Therefore, an abnormal intestinal permeability may not be the cause of ASCA positivity in patients with CD.
Jaya Benjamin MSc*, Govind K. Makharia DM*, Yogendra K. Joshi PhD*, * Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari nagar, New Delhi, India.