• Celiac Disease in at Risk Groups in Southern California

      Pietzak, Michelle; Wolfe, Adam; Rongey, Christine; Monarch, Elaine; Bergwerk, Ari; Duh, Glenn; Naon, Hillel; Quiros, Antonio; Sinatra, Frank Raymond, M.D.; Yamaga, Ardath; et al. (2002)
    • Effect Of the Gluten Free Diet on Serum Zonulin Levels and Autoimmune Biomarkers in Both Treated and Untreated Celiac Disease Patients

      Kryszak, Deborah; Neri, Elena; Palese, Teresa; Sapone, Anna; Counts, Donald R.; Not, Tarcisio; Catassi, C. (Carlo); Fasano, Alessio (2005)
      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.
    • Inhibition of the zonulin pathway blocks the progression from pre-clinical autoimmunity to Type 1 diabetes in BB/wor rats

      Fasano, Alessio (2005)
      Background: We have previously studied that zonulin, a protein involved in tight junctions modulation, is up regulated in BB/wor rats and is responsible for the increased intestinal permeability (IP) typical of this animal model of autoimmunity. We have also demonstrated that by blocking the zonulin pathway before the onset of autoimmunity, the incidence of Type 1 Diabetes (T1D) can be prevented in 75% of the animals. Aim : To determine whether the progression of T1D can be blocked, even though the autoimmune process is already established. Methods: 30 BB/ Wor rats were randomized after immune seroconversion (average age 55 days) in a treatment group (N=20) that received autoclaved water supplemented with 3mg /ml of zonulin receptor blocker AT1001 and HCO3- 1.5g/100ml to buffer gastric acidity, and a placebo group (N=10) that received only water with HCO3-. Serum zonulin and autoantibody levels were monitored at the beginning of the study and at its endpoint. Water intake was monitored daily, weight gain and serum glucose levels were checked weekly. Rats with fasting blood glucose  250 mg/dl were considered diabetic and were sacrificed within 24 hours of reaching the diabetic status. Results: Six out of 10 (60%) untreated rats developed T1D, while only 7/20 (35%) of the AT1001-treated animal progressed to T1D. The average age of onset of T1D was 85.410.4 in the placebo group and 86.010.3 in the treated group. AT1001 treatment did not change the serum zonulin levels between beginning (average age 55 days) and the endpoint of the experiment (average age 100 days) of the experiments. Conversely, the anti-glutamic acid decarboxylase (GAD) antibodies were significantly reduced in AT1001-treated rats that did not develop T1D (0.870.35) compared to the treated animals with the disease developed (1.870.59; p<0.05) Conclusions: The blockage of the zonulin pathway in BB/wor rats at their preclinical autoimmune stage significantly reduced the progression to T1D. This decreased incidence of T1D was associated to a significant reduction of the anti-GAD antibodies following AT1001 treatment.
    • The Natural History of Undiagnosed Celiac Disease: A Retrospective Study

      Sturgeon, Craig; Bhatti, Bushra; Kryszak, Deborah; Catassi, C. (Carlo); Helzlsouer, Kathy; Clipp, Sandra L.; Fasano, Alessio (2009)
    • Potential Celiac Disease (CD) in Chilcdren with CD Family Risk: Clinical Correlates and Outcome

      Catassi, C. (Carlo); Lionetti, Elena; Castellaneta, Stefania; Pulvirenti, Alfredo; Tonutti, Elio; Francavilla, Ruggiero; Fasano, Alessio; The Italian working group on weaning and CD risk (SIGENP) (2012)
    • Retrospective Study of the Natural Long-Term History of Untreated Celiac Disease

      Kryszak, Deborah; Bhatti, Bushra; Sturgeon, Craig; Catassi, C. (Carlo); Helzlsouer, Kathy; Clipp, Sandra L.; Fasano, Alessio (2009)