Anti-Saccharomyces cerevisiae antibodies in first-degree relatives of celiac disease patients.

To the Editor: Anti-Saccharomyces cerevisiae antibodies (ASCA) are considered as a marker of Crohn’s disease (CD) being associated with small bowel disease, fibrostenosis, internal perforations, and small bowel surgery. However, the cause of ASCA positivity is still unknown and some authors have considered antibody formation as a consequence of increased mucosal permeability. These antibodies are also found in 10% to 20% of first-degree relatives of CD patients and in 0% to 5% of the general population. Several authors demonstrated increased permeability of the gut mucosa in celiac disease (CeD) patients and their relatives, with or without symptoms, by sugar absorption tests. Probably this condition is implicated to constitutional factors in susceptible individuals and may help in detecting latent CeD. The presence of ASCA has been described in the sera of CeD patients, suggesting that these antibodies can be a sensitive marker of intestinal mucosa integrity not only in CD. To our knowledge, ASCA has not been evaluated in the serum of relatives of CeD patients. In this study, 57 healthy individuals, 38 females (66.7%), and 19 males (33.3%), mean age 38.9 years (range, 14-67y) were enrolled as a comparison group, all negative to endomysial (IgA-EmA) and antitissue transglutaminase (IgA anti-tTG) antibodies. In all, 76 first-degree relatives of the CeD patients, 50 (65.8%) females and 26 (34.2%) males, mean age 38.7 years (range, 5-83y) were included in the study. They were classified according to the presence of EmA and/or tTG antibodies in the sera: 46 individuals were negative for both antibodies (group RI) and 30 individuals were positive for at least one of them (group RII): 10 positive for both EmA and anti-tTG, 6 positive only for EmA, and 14 positive only for anti-tTG. Differences between the variables were evaluated by Fisher exact test: P values <0.05 were considered statistically significant. ASCA IgA was found in 5.2% of controls, 8.7% of RI, and 23.3% of RII individuals, whereas for ASCA IgG it was 1.7%, 4.3%, and 23.3%, respectively. Both ASCA IgA and IgG were present in 2.2% of RI and 10.0% of RII individuals. Statistical analysis showed no significant difference between controls and RI (ASCA IgA P=0.69; ASCA IgG P=0.58). However, among controls and RII, significant differences were observed (ASCA IgA P=0.028; ASCA IgG P=0.002; ASCA IgA/IgG P=0.038). When comparing RI and RII groups, significant difference (P=0.024) was observed in only ASCA IgG. The high prevalence of ASCA (specifically class IgG) in CeD patients has been reported, probably due to the fact that they had been longer exposed to gluten and therefore had more long-lasting damage. Additionally, according to Mallent-Hent et al, ASCA levels have been helpful in monitoring CeD patients for compliance to the gluten-free diet, demonstrating recovery of the mucosa. However, the positivity detected in the relatives of CeD patients leads us to suggest that ASCA does not differentiate CD from CeD. CeD is a familial disease and oligosymptomatic forms frequently occurs among the first-degree relatives of CeD patients. Corroborating, in the present investigation, in group RI, in which no CeD markers were detected, ASCA IgA and IgG were similar to the control group, whereas the levels of these antibodies increased in relatives who were positive for IgA-EmA and/or anti-tTG (group RII). These data allow us to demonstrate for the first time that ASCA is also present in the relatives of CeD patients. One question addressed by our study is that the levels of ASCA are not only disease associated, but represent a familial immunologic trait expressed in CeD patients. In many cases, increased intestinal permeability seems to precede disease and causes an abnormality in antigen delivery that triggers the injury process, leading to the autoimmune response. This can justify the presence of ASCA in asymptomatic relatives of CeD patients. In conclusion, the results showed that ASCA levels are increased in family members of CeD patients positive for EmA and/or anti-tTG, probably due to genetic factors and increased intestinal permeability.