Celiac disease: From gluten to autoimmunity Chiara Briani a , Diana Samaroo b , Armin Alaedini b, ⁎ a Department of Neurosciences, University of Padova, Padova, Italy b Department of Neurology and Neuroscience, Cornell University, New York, NY, USA article info abstract Article history: Received 2 May 2008 Accepted 20 May 2008 Available online 25 June 2008 Celiac disease, also known as gluten-sensitive enteropathy and nontropical sprue, is a prevalent autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins of rye and barley in genetically susceptible individuals. The immune response in celiac disease involves the adaptive, as well as the innate, and is characterized by the presence of anti-gluten and anti-transglutaminase 2 antibodies, lymphocytic infiltration in the epithelial membrane and the lamina propria, and expression of multiple cytokines and other signaling proteins. The disease leads to inflammation, villous atrophy, and crypt hyperplasia in the small intestine. In addition to the intestinal symptoms, celiac disease is associated with various extra-intestinal complications, including bone and skin disease, anemia, endocrine disorders, and neurologic deficits. Gluten-free diet is currently the only effective mode of treatment for celiac disease, but better understanding of the mechanism of the disease is likely to add other choices for therapy in the future. © 2008 Elsevier B.V. All rights reserved. Keywords: Celiac disease Gluten Transglutaminase Gliadin Antibodies Diet Contents 1. Epidemiology and genetics of celiac disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645 2. Clinical presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645 2.1. Dermatitis herpetiformis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645 2.2. Neurologic disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645 2.3. Endocrine disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 645 2.4. Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646 3. Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646 3.1. Serologic tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646 3.2. Intestinal biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 4. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 5. Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 647 6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649 . Take-home messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 649 The earliest known descriptions of symptoms consistent with celiac disease were by the Greek physician Aretaeus in the second century. In the 19th century, Samuel Gee and other physicians further defined the symptoms and characteristics of the disease and offered various ideas about treatment. However, Willem Karel Dicke was the first to recognize the Autoimmunity Reviews 7 (2008) 644–650 ⁎ Corresponding author. 1300 York Avenue, LC819, Department of Neurology and Neuroscience, Cornell University, New York, NY, 10065, USA. Tel.: +1 212 7467841; fax: +1 212 7468532. E-mail address: ara2004@med.cornell.edu (A. Alaedini). 1568-9972/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.autrev.2008.05.006 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev