Systemic Autoimmune Disorders in Celiac Disease

Alessio Fasano

Disclosures

Curr Opin Gastroenterol. 2006;22(6):674-679. 

In This Article

Autoimmune Diseases Associated with Celiac Disease

The celiac disease-associated autoimmune disorders can be either organ-specific, in which the autoantibodies are specifically directed against antigens localized in a particular organ and are often detected in circulation (e.g. Hashimoto's thyroiditis and T1D), or nonorgan-specific autoimmune disorders characterized by the presence of autoantibodies directed against ubiquitous antigens (e.g. systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and scleroderma).[14] The focus of this review will be on the celiac disease-organ-specific autoimmune disorders association, since this association has been extensively studied.

A 10-year, age-matched study[15] found a highly significant correlation between endocrine disorders in celiac disease patients versus controls and concluded that celiac disease patients have a significantly higher prevalence of T1D. More recent studies[16,17] show a similar incidence of celiac disease in T1D patients. Early identification of celiac disease and subsequent treatment improves growth and diabetic control in children with T1D.[18,19] This comorbidity suggests possible genetic polymorphisms that may dictate the risk of celiac disease in subjects with T1D. To address this hypothesis, Sumnik et al. [20*] investigated whether the susceptibility to celiac disease in diabetic children is modified by positivity for HLA-DQB1*02-DQA1*05 and DQB1*0302-DQA1*03, and by alleles of single nucleotide polymorphisms within the genes encoding several cytokines. The authors compared genotypic data between 130 case subjects (children with T1D and celiac disease) and 245 control subjects (children with T1D only). The best-fitting model showed that risk of celiac disease is increased by presence of HLA-DQB1*02-DQA1*05 [odds ratio 4.5 (95% confidence interval 1.8-11) for homozygosity and 2.0 (1.1-3.7) for a single dose] and also independently by tumor necrosis factor -308A [1.9 (1.1-3.2) for phenotypic positivity], whereas interleukin-1α -889T showed a weak negative association [0.6 (0.4-0.9)].[20*] These results indicate that the risk of celiac disease in children with T1D is significantly modified both by the presence of HLA-DQB1*02-DQA1*05 and by a variant of another gene within the major histocompatibility complex, i.e. tumor necrosis factor -308A.

Thyroiditis has been repeatedly associated with celiac disease.[15,21,22,23] A highly significant association exists between celiac disease and autoimmune thyroiditis (Graves' disease and Hashimoto's thyroiditis), as evidenced by elevated EMA antibodies in these thyroid conditions.[23] In addition, abnormal liver enzymes (transaminases) are common in both thyroid disorders and subclinical celiac disease.[24] Mainardi et al.[25] specifically studied the association of celiac disease with autoimmune thyroid disease. The authors evaluated the prevalence of celiac disease in 100 patients with thyroid autoimmunity (TAI). They found that the prevalence of celiac disease in patients affected by autoimmune thyroid disease was 2% and that the serologic markers for celiac disease became undetectable 6 months after beginning a GFD, while thyroid autoantibodies did not change following the implementation of the diet. More recently, da Silva et al.[26] have studied 52 patients with celiac disease, nine of which were on a GFD. The patients were divided into four groups: Group 1, without thyroid involvement (n = 30), and Groups 2A-C, with thyroid involvement (n = 22) [Group 2A, subclinical hypothyroidism (n = 11); Group 2B, clinical hypothyroidism (n = 10) and Group 2C, other thyroid disorders (n = 1)]. Increased levels of thyroid-stimulating hormone and/or anti-thyroperoxidase antibodies were detected in Groups 2A (21.1%) and 2B (19.2%). The patients of Group 2B presented clinical symptoms of hypothyroidism before the diagnosis of celiac disease and five of these patients were receiving levothyroxine. There was a statistically significant correlation between the age when thyroid disease was diagnosed (current age) and the age of celiac disease diagnosis when Groups 1 and 2B were compared. Patients with thyroid involvement presented associated diseases such as T1D, Down's syndrome, ulcerative colitis and dermatitis herpetiformis.

Different conclusions were reached by Sumnik et al.,[27] who performed a multicenter retrospective case-control study comparing data from 84 diabetic children with celiac disease (Group 1) to 167 diabetic children without celiac disease (Group 2), matched by age at T1D onset, duration of T1D and center. Markers of TAI, thyroid function and HbA1c were recorded. The TAI follow-up lasted 4.9 ± 2.8 years. TAI was diagnosed in 13% of children in Group 1 and 19% of children in Group 2. Diabetes control was not influenced by TAI in either group.[27] These results prompted the authors to conclude that occurrence of TAI in diabetic children is not related to coexisting celiac disease.

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