Celiac Disease-Associated Autoimmune Endocrinopathies

Abstract

3Celiac disease (CD) is an autoimmune disorder induced by gluten intake in genetically susceptible individuals. It is characterized by the presence of serum antibodies to endomysium, reticulin, gliadin, and tissue transglutaminase. The incidence of CD in various autoimmune disorders is increased 10-to 30-fold in comparison to the general population, although in many cases CD is clinically asymptomatic or silent. The identification of such cases with CD is important since it may help in the control of type I diabetes or endocrine functions in general, as well as in the prevention of long-term complications of CD, such as lymphoma. It is believed that CD may predispose an individual to other autoimmune disorders such as type I diabetes, autoimmune thyroid, and other endocrine diseases and that gluten may be a possible trigger. The onset of type I diabetes at an early age in patients with CD, compared to non-CD, and the prevention or delay in onset of diabetes by gluten-free diet in genetically predisposed individuals substantiates this antigen trigger hypothesis. Early identification of CD patients in highly susceptible population may result in the treatment of subclinical CD and improved control of associated disorders.Autoimmunity as a concept evolved from the beginning of this century, when Ehrlich and Morgenroth (26) introduced the phenomenon of "horror autotoxicus," i.e., fear of selfpoisoning. Subsequently, many diseases were recognized with etiology arising from the abnormal reaction of the immune system to self antigens. These observations laid the foundation for establishing postulates that are characteristic of an autoimmune disease (4, 7). Since then, several hypotheses have been put forward regarding the mechanisms of autoimmunity (22,76,84,110,118).In general, autoimmune disorders can be classified as either organ specific or non-organ specific. In organ-specific autoimmune diseases, the autoantibodies are specifically directed against antigens localized in a particular organ and are often detected in circulation. Examples of organ-specific autoimmunity include Hashimoto's thyroiditis, type I diabetes, and myasthenia gravis.In contrast, the non-organ-specific autoimmune disorders are characterized by the presence of autoantibodies directed against ubiquitous antigens (not specific to a particular organ). This results in the involvement of several organs and is often characterized by the presence of specific circulating immune complexes. Non-organ-specific autoimmunity includes diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and scleroderma.Epidemiologic studies have shown that genetic factors are involved in host susceptibility to autoimmune disease. For example, the concordance rate of a particular autoimmune diseases is much higher in monozygotic twins in comparison to fraternal twins (17). Moreover, this incidence is much higher in organ-specific autoimmune disorders in comparison to nonorgan-specific disorders. Thus, in Grave's thyrotoxicosis, Hashimoto's disease, a...

Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats

“…Restriction of gluten reverses small intestinal epithelial damage, restores tj integrity, serum zonulin levels are reduced and intestinal permeability returns to baseline (A.F, unpublished data). CD and T1D are comorbid diseases, as the prevalence of CD among patients with T1D is 6-to 9-fold higher than the general population (29,30). Two independent studies tracking large cohorts of newborns at high risk for T1D showed that the odds ratio for developing the disease was 4-to 5-fold higher in subjects prematurely exposed (Ͻ3 months of age) to gluten (31,32).…”

Affinity maturation of immunoglobulin A anti-tissue transglutaminase autoantibodies during development of coeliac disease

“…In children who were diagnosed with CD, the average number of samples studied, with standard deviation (s.d.) and range in parenthesis, was 11·8 (Ϯ3·9; [7][8][9][10][11][12][13][14][15][16][17][18][19], and for the children with transient or fluctuating values, 14·1 (Ϯ4·0; [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. At the time of the diagnosis of CD, children were of a mean age of 4·4 (Ϯ1·3; 3·1-6·7) years.…”

Hypoparathyroidism and coeliac disease: a potentially dangerous combination

“…On the other hand, tissue transglutaminase antibodies produced in coeliac disease have been shown to cross-react with other antigens and endomysial antibody reactions on parathyroid tissue have been shown to lead to parathyroid atrophy. 12,13 Postoperative hypoparathyroidism may also coexist with coeliac disease, as described in the two patients mentioned above.…”