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Dietary Gluten

Tissue Tranglutaminase (tTGA)

Deaminated Gluten/tTGA

Antigen Presenting Cells

Anti-Gluten and Anti- tTGA IgG and IgA

Activated T-Cells

Mucosal Damage

Symptoms

Figure III-1. Mechanism of Celiac Disease

C. Range of Adverse Effects The clinical manifestations of celiac disease are highly variable in character and severity. The reasons for this diversity are unknown but may depend on the age and immunological status of the individual, the amount, duration, or timing of exposure to gluten, and the specific area and extent of the gastrointestinal tract involved by disease (Dewar et al., 2004). These clinical manifestations can be divided into gastrointestinal, or “classic,” and non-gastrointestinal manifestations. Gastrointestinal manifestations usually present in children 4 to 24 months old and include abdominal pain and cramping, bloating, recurrent or chronic diarrhea in association with weight loss, poor growth, nutrient deficiency, and (in rare cases) a life-threatening metabolic emergency termed celiac crisis, characterized by hypokalemia and acidosis secondary to profuse diarrhea (Farrell and Kelly, 2002; Baranwal et al., 2003). Non-gastrointestinal manifestations are more insidious and highly variable and are the common presenting signs in older children and adults. These manifestations are frequently the result of long-term nutrient malabsorption, including iron deficiency anemia, short stature, delayed puberty, infertility, and osteoporosis or osteopenia (Fasano, 2003). In children, progressive malabsorption of nutrients may lead to growth, developmental, or neurological delays (Catassi and Fasano, 2004). Extra-intestinal manifestations such as dermatitis herpetiformis, hepatitis, peripheral neuropathy, ataxia, and epilepsy have also been associated with celiac disease (Fasano and Catassi, 2001). Individuals with untreated celiac disease are also at increased risk for potentially serious medical conditions, such as other autoimmune diseases (e.g., Type I diabetes mellitus) and intestinal cancers associated with high mortality (Farrell and Kelly, 2002; Peters et al., 2003; Catassi et al., 2002). For example, individuals with celiac disease have an 80-fold greater risk of developing adenocarcinoma of the small intestine, a greater than two-fold increased risk for intestinal or extraintestinal lymphomas (Green and Jabri, 2003) and a 20-fold greater risk of developing enteropathy-associated T cell lymphoma (EATL) (Catassi et al.,

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