Celiac Disease and Gluten

Multidisciplinary Challenges and Opportunities

Peter Koehler, Herbert Wieser, Katharina Konitzer

• Publisher: Academic Press
• Year: 2014
• Print ISBN: 9780124202207
• eBook ISBN: 9780127999265
• Topic: Technology & Engineering
• Subtopic: Pharmacology
• Index: Technology & Engineering

Celiac Disease and Gluten: Multidisciplinary Challenges and Opportunities is a unique reference work—the first to integrate the insights of the causes and effects of celiac disease from the chemistry of reaction-causing foods to the diagnosis, pathogenesis, and symptoms that lead to proper diagnoses and treatment. With an estimated three million people in the United States alone affected by celiac disease, an autoimmune digestive disease, only five percent are properly diagnosed. Drawing on the connection between foods containing gluten and the resulting symptoms, this resource offers distinctive information that directly explores and links food science, medical diagnostics, and treatment information. A helpful tool for researchers and medical practitioners alike, Celiac Disease and Gluten: Multidisciplinary Challenges and Opportunities helps refine research targets, and provides a comprehensive overview on the multidisciplinary approaches to all crucial aspects related to celiac disease. - Presents key information from medical and food science research, as well as provides clinical insights - Provides direct corollary insights between source and symptom - Written by experts whose detailed experiments and results have shaped our understanding of celiac disease

Chapter 1

Celiac Disease—A Complex Disorder

Abstract

Celiac disease (CD) is defined as a chronic immune-mediated enteropathy precipitated by exposure to dietary gluten (storage proteins of wheat, rye, barley, and oats) in genetically predisposed individuals. Recent epidemiologic data suggest a prevalence of approximately 1% in most Western countries. The genetic predisposition includes human leukocyte antigen (HLA) DQ2 and DQ8 genes as major factors and a number of non-HLA genes. In addition to gluten, other environmental triggers such as pathogenic microorganisms, timing of gluten introduction, and breastfeeding may be important for disease development. CD is classically characterized by small intestinal villous atrophy, crypt hyperplasia, and increased lymphocyte infiltration. The clinical features of CD include both intestinal symptoms, such as diarrhea or steatorrhea, as well as extraintestinal symptoms, such as bone pain or osteoporosis. CD is frequently associated with autoimmune diseases, such as type 1 diabetes, and neurological and psychiatric complaints, such as schizophrenia. Further gluten-related disorders are dermatitis herpetiformis, gluten ataxia, wheat-dependent exercise-induced anaphylaxis, non-celiac gluten sensitivity, and irritable bowel syndrome. The diagnostic scheme of CD is usually based on symptoms typical of CD, testing of serum antibodies, and histological judgment of small intestinal biopsies. The complex pathomechanism of CD consists of incomplete digestion of gluten, para- and transcellular passage of gluten peptides through the epithelium, and immune responses in the lamina propria. The adaptive immunity includes the deamidation and transamidation of gluten peptides by tissue transglutaminase, their binding to HLA-DQ molecules, their presentation to T cells, and the subsequent delivery of damaging cytokines and chemokines. Additionally, antibodies against gluten peptides and autoantibodies against transglutaminase are produced by B cells. The adaptive immunity is accompanied by the innate immunity characterized by the production of interleukin 15 and the expansion of intraepithelial lymphocytes.

Keywords

Celiac disease; Diagnosis; Digestion; Environmental factors; Epidemiology; Genetics; Gluten; Immune response; Small intestine; Symptoms

Chapter Outline

1. History 2

2. Epidemiology 4

3. Genetics and Environmental Factors 7

3.1 Genetics 8

3.2 Potential Environmental Factors Beside Gluten 10

3.3 Interplay Between Genetics and the Environment 12

4. Clinical Features 13

4.1 Symptoms 13

4.2 Pathology 16

4.3 Serology 19

4.4 Refractory Celiac Disease 21

4.5 Other Gluten-Related Disorders 23

4.5.1 Dermatitis Herpetiformis 24

4.5.2 Gluten Ataxia 25

4.5.3 Wheat Allergy 26

4.5.4 Non-Celiac Gluten Sensitivity 26

4.5.5 Irritable Bowel Syndrome 28

4.6 Associated Diseases 28

5. Diagnosis 30

5.1 Serological Tests 34

5.2 Small Intestinal Biopsy 39

5.3 HLA-DQ Tests 42

6. Pathomechanism 43

6.1 Gluten Intake and Digestion 43

6.2 Epithelial Passage 49

6.3 Immune Response 53

6.3.1 Adaptive Response 54

6.3.2 Innate Response 71

6.4 Concluding Remarks 74

References 75

1. History

Until the Neolithic age, humans were not exposed to gluten for hundreds of thousands of years. Only about 10,000 years ago, cereal farming started in the Middle East, including the Tigris, Euphrates, and Upper Nile regions, and gradually spread across Europe with wheat and barley as prominent crops. The process of breadmaking was developed in Egypt about 5000 years ago and transferred via Greece to the Romans and then to other European regions. Wheat and rye bread became a staple food for Western populations; consequently, gluten consumption increased enormously. It appears that many individuals did not adapt to this “new” food item and did not develop an immunological tolerance [1].

Aretaeus of Cappadocia, a Greek physician practicing in Rome and Alexandria in the first and second centuries AD, was the first to describe an intestinal disorder similar to the picture of celiac disease (CD) nowadays. It was a general report on patients with chronic diarrhea, but some passages suggest that CD patients were among them. He wrote: “If diarrhea does not proceed from a slight cause of only one or two days duration, and if, in addition, the general system be debilitated by atrophy of the body, the celiac sprue of chronic nature is formed.” He called these patients “koiliakos” according to the Greek term “koilia”, which simply means abdomen. He believed the disease to be caused by partial indigestion of food, which should be treated by relieving the bowel of stress by rest and fasting. The case of a first century AD young woman, found in the archaeological site of Cosa, impressively demonstrated that a CD-like disorder existed in antiquity [2,3]. She was characterized by clinical signs of malnutrition, such as short height, osteoporosis, dental enamel hypoplasia, and indirect signs of anemia, which are all strongly suggestive for CD. Deoxyribonucleic acid (DNA) from bone and tooth followed by human leukocyte antigen (HLA)-typing displayed HLA-DQ2.5, the haplotype associated with the highest risk of CD (see Section 3.1).

It was not until the year 1888 that Samuel Gee, an English physician and pediatrician, presented the first accurate description of the clinical syndrome of CD. He used the term “celiac affection” and defined the disease as “a kind of chronic indigestion, which is met within persons of all ages, yet especially occurs in children between one and five years ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Biography
• Frequent Abbreviations
• Introduction
• Definitions and Terms
• Chapter 1. Celiac Disease—A Complex Disorder
• Chapter 2. Gluten—The Precipitating Factor
• Chapter 3. Treatment of Celiac Disease
• Chapter 4. Gluten-Free Products
• Future Tasks
• Further Reading
• Index
• Color Plates