Effect Of the Gluten Free Diet on Serum Zonulin Levels and Autoimmune Biomarkers in Both Treated and Untreated Celiac Disease Patients

Abstract

Background: It is well known that Celiac Disease (CD) can be associated with other autoimmune diseases (AD). It is however still unclear whether the CD-associated risk of other AD is related to ongoing gluten ingestion or simply depends on common genetic background. Zonulin, which is responsible for the modulation of intestinal permeability, is up regulated in CD and other AD, such as Type 1 diabetes. Our hypothesis is that the loss of barrier function secondary to zonulin increase in CD can be involved in the high risk for AD co-morbidity. Aim: To establish the changes of serum zonulin levels and serum autoimmune antibodies in patients with newly diagnosed CD and after treatment with the gluten-free diet (GFD). Patients and Methods: They were 54 patients diagnosed with CD (20 M and 34 F; mean age: 39y; biopsy-proven: 42/54). Associated AD were found in 8 subjects (2 Type 1 diabetes, 1 Graves’s disease, 5 rheumatoid arthritis). Serum samples were collected at diagnoses and after a mean period of 17 months of GFD (range 10-49). All serum samples were measured for auto-antibodies related to CD (anti-transglutaminase - tTG, anti-endomysial - EMA), Type 1 diabetes (IA-2: tyrosine phosphates, IAA: anti-insulin antibodies, GAD: glutamic acid decarboxilase), thyroiditis (TPO: thyreoperoxidase antibodies, TG: thyreoglobulin antibodies), and zonulin levels. Results: at CD diagnosis increased serum zonulin were found in 76 % and auto-antibodies were detected in 39 % (TPO: 21.7%, TG 19.6%, GAD 6.5%, ICA 4.4% and IA-2 2.5 %). After GFD, EMA and zonulin remained altered in 13% of patients, and tTG in 35% of the subjects. Some auto-antibodies decreased (TPO: 10.9%, GAD 4.4%), while other remained unchanged (TG 23.9%, ICA 4.4%, and IA-2 2.2 %). Seven out of 53 patients did not start the GFD. These subjects had altered zonulin, EMA, and tTG and 14% of them were auto-antibodies positive. In these subjects, both zonulin levels and serum auto-antibodies did not change at the follow-up evaluation. Conclusions: Untreated CD typically show zonulin up-regulation and increased prevalence of serum auto-antibodies. After treatment with GFD, serum zonulin levels tend to normalize, a situation that is associated with a decreased prevalence of some auto-antibodies (especially TPO). These results indirectly suggest that recovery of the intestinal barrier function can decrease the risk of associated autoimmune phenomena. These results also suggest that if the GFD is implemented early (less 30 years of age) the auto-antibodies will seroconvert, suggesting a possible protective roll against autoimmunity co-morbidity, if CD is diagnosed early and started on a GFD.