Systemic Autoimmune Disorders in Celiac Disease
Systemic Autoimmune Disorders in Celiac Disease
Purpose of Review: Celiac disease is an immune-mediated disorder clinically characterized by a multitude of symptoms and complications. The comorbidity between celiac disease and other autoimmune disorders has been clearly established.
Recent Findings: Two main theories have been postulated to explain this comorbidity: (1) linkage disequilibrium between the genes responsible for celiac disease and those responsible for the coexpressed autoimmune diseases or (2) untreated celiac disease leading to the onset of other autoimmune diseases. This article reviews the current literature supporting either theory and places the current knowledge in the field within the context of the most recent data on the pathogenesis of celiac disease.
Summary: The current literature did not clearly establish which of the two theories explain the comorbidity between celiac disease and other autoimmune disorders. There is, however, growing evidence that the loss of the intestinal barrier function typical of celiac disease could be responsible of the onset of other autoimmune disease. This concept implies that the autoimmune response can be theoretically stopped and perhaps reversed if the interplay between autoimmune predisposing genes and trigger(s) is prevented or eliminated by a prompt diagnosis and treatment.
Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye and barley) in genetically susceptible persons. Celiac disease has several autoimmune features, including the production of highly disease-specific IgA and IgG autoantibodies to tissue transglutaminase (tTG) when patients are on a gluten-containing diet, and the presence of small intestinal intraepithelial lymphocytes which can mediate direct cytotoxicity of enterocytes expressing MIC molecules in an antigen-nonspecific manner. Similar to typical autoimmune disorders, celiac disease has a multifactorial etiology with complex genetics and comorbidity with autoimmune diseases. Celiac disease is, however, a unique example of autoimmunity, since early serological diagnosis and dietary treatment can revert the autoimmune process and can prevent its severe, sometimes life-threatening complications. Therefore, the common wisdom among experts in the field supports the notion that individuals affected by celiac disease should be treated, irrespective of the presence of symptoms and/or associated conditions. Well-designed prospective clinical studies to address this point have, however, not been performed, nor can they be conceived, given the ethical implications of such a proposition. Celiac disease can manifest itself with a previously unappreciated range of clinical presentations (the so-called celiac iceberg, Fig. 1), including the typical malabsorption syndrome (chronic diarrhea, weight loss, abdominal distension) and a spectrum of symptoms potentially affecting any organ system. Since celiac disease often presents in an atypical or even silent manner, many cases remain undiagnosed, their diet treatment is significantly delayed and, consequently, the risk of long-term complications increases. While evidence-based data support the causative effect of untreated celiac disease for some of these complications, for other conditions this association remains questionable. One of the most controversial issues concerning possible complications of untreated celiac disease involves the association between celiac disease and other autoimmune disorders.
(Enlarge Image)
The celiac iceberg. The clinical outcome of the interplay between celiac disease genetic makeup and exposure to gluten, the environmental trigger of the disease, is typically represented by the iceberg model, with the symptomatic forms present at the visible part of the iceberg and the silent and potential forms being submerged below the water line.
Purpose of Review: Celiac disease is an immune-mediated disorder clinically characterized by a multitude of symptoms and complications. The comorbidity between celiac disease and other autoimmune disorders has been clearly established.
Recent Findings: Two main theories have been postulated to explain this comorbidity: (1) linkage disequilibrium between the genes responsible for celiac disease and those responsible for the coexpressed autoimmune diseases or (2) untreated celiac disease leading to the onset of other autoimmune diseases. This article reviews the current literature supporting either theory and places the current knowledge in the field within the context of the most recent data on the pathogenesis of celiac disease.
Summary: The current literature did not clearly establish which of the two theories explain the comorbidity between celiac disease and other autoimmune disorders. There is, however, growing evidence that the loss of the intestinal barrier function typical of celiac disease could be responsible of the onset of other autoimmune disease. This concept implies that the autoimmune response can be theoretically stopped and perhaps reversed if the interplay between autoimmune predisposing genes and trigger(s) is prevented or eliminated by a prompt diagnosis and treatment.
Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye and barley) in genetically susceptible persons. Celiac disease has several autoimmune features, including the production of highly disease-specific IgA and IgG autoantibodies to tissue transglutaminase (tTG) when patients are on a gluten-containing diet, and the presence of small intestinal intraepithelial lymphocytes which can mediate direct cytotoxicity of enterocytes expressing MIC molecules in an antigen-nonspecific manner. Similar to typical autoimmune disorders, celiac disease has a multifactorial etiology with complex genetics and comorbidity with autoimmune diseases. Celiac disease is, however, a unique example of autoimmunity, since early serological diagnosis and dietary treatment can revert the autoimmune process and can prevent its severe, sometimes life-threatening complications. Therefore, the common wisdom among experts in the field supports the notion that individuals affected by celiac disease should be treated, irrespective of the presence of symptoms and/or associated conditions. Well-designed prospective clinical studies to address this point have, however, not been performed, nor can they be conceived, given the ethical implications of such a proposition. Celiac disease can manifest itself with a previously unappreciated range of clinical presentations (the so-called celiac iceberg, Fig. 1), including the typical malabsorption syndrome (chronic diarrhea, weight loss, abdominal distension) and a spectrum of symptoms potentially affecting any organ system. Since celiac disease often presents in an atypical or even silent manner, many cases remain undiagnosed, their diet treatment is significantly delayed and, consequently, the risk of long-term complications increases. While evidence-based data support the causative effect of untreated celiac disease for some of these complications, for other conditions this association remains questionable. One of the most controversial issues concerning possible complications of untreated celiac disease involves the association between celiac disease and other autoimmune disorders.
(Enlarge Image)
The celiac iceberg. The clinical outcome of the interplay between celiac disease genetic makeup and exposure to gluten, the environmental trigger of the disease, is typically represented by the iceberg model, with the symptomatic forms present at the visible part of the iceberg and the silent and potential forms being submerged below the water line.
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