Preface

Chapter 7 **Examining Non‐Celiac Consumers of Gluten‐Free Products: An**

Tiziana de‐Magistris, Hind Belarbi and Wajdi Hellali

Ricardo Fueyo-Díaz, Santiago Gascón-Santos and Rosa Magallón-

**Empirical Evidence in Spain 101**

Botaya

**VI** Contents

Chapter 8 **I Can't Eat That! Sticking to a Gluten-Free Diet 115**

**Celiac disease (CD**) is described as a chronic, genetically based gluten-sensitive immunemediated enteropathic disease, primarily affecting the small intestinal mucosa. CD did not occur before the Neolithic period (beginning about 9500 BC) because the grains have been cultivated by humans only since this time, in the Fertile Crescent in Western Asia.

In 1930, during World War II, a Dutch pediatrician William Dicke observed that a lack of access to wheat improved the status of children with celiac disease, and in 1952, he was ac‐ knowledged for linking the ingestion of wheat proteins as the cause of celiac disease. The first biopsy technique of CD was developed by Margot Shiner, a pediatric gastroenterologist in 1950; she observed the small intestine and the pathologic changes in the celiac disease.

In 1966, dermatitis herpetiformis was linked to gluten sensitivity. In the 1980s, celiac disease was associated with other autoimmune diseases such as thyroid diseases, type 1 diabetes mellitus, and Down syndrome. In the 1990s, genetic markers HLA-DQ2 and HLA-DQ8 and the antitransglutaminase antibodies were identified.

The prevalence of CD is approximately 1% within the US and European populations and may be higher in Northern European countries, approximately 1.5%. CD is a common disor‐ der in North Africa, the Middle East, and India. The diagnostic rate is low in these countries due to low availability of diagnostic facilities and poor disease awareness. The highest CD prevalence in the world (5.6%) has been described in an African population originally living in Western Sahara, the Saharawi, of the Arab-Berber origin.

Initially, it was thought that exogenous gluten products were directly toxic to the mucosa in celiac disease. In contrast with earlier suggestions, intraepithelial lymphocytes (IELs) are now thought to actively contribute to mucosal damage. Antigen exposure in celiac disease causes rapid in situ activation of α/β T-cell IELs. These cells may then damage enterocytes through contributions from several possible mechanisms, including the NKG2D-major his‐ tocompatibility complex class I chain-related gene A pathway.

CD diagnosis includes three major steps: (1) blood tests (including serology) positive, (2) small bowel biopsy and histological confirmation, and (3) implementation and response to a gluten-free diet (GFD). At present, the only effective treatment available for CD individuals is a strict lifelong gluten-free diet (GFD). There is a need for an alternative, because GFD is costly and not universally available and compliance is difficult.

**Non-celiac gluten sensitivity (NCGS):** It is a new syndrome of gluten intolerance, a condi‐ tion where intestinal and extraintestinal symptoms are triggered by gluten ingestion, in the absence of CD and wheat allergy, as defined by discussions held at three different interna‐ tional consensus conferences. The clinical picture of NCGS is a combination of IBS-like

symptoms, behavior disturbances, and systemic manifestations. In the medical literature, some other names have been suggested for this disorder, such as gluten sensitivity (GS), gluten hypersensitivity, or nonceliac gluten intolerance.

This new entity was described around 30 years ago, but it was necessary to wait until 2011, when it was proposed by members of the First Expert Meeting on gluten sensitivity. The new defini‐ tion (the Oslo definition) of CD suggested that the disorder should be named NCGS, which made it distinguishable from CD. The Second Expert Meeting on GS that was held in Munich in 2012 decided to change the name of this disorder to NCGS in order to avoid confusion with CD. The first case reports of NCGS in children were described in 2012. NCGS can be diagnosed in those patients with gluten intolerance who do not develop antibodies that are typical neither of CD nor of wheat allergy (WA) and who do not suffer from lesions in the duodenal mucosa, which are characteristic of CD. The gluten-free diet leads to complete regression of symptoms in the same way and efficacy that is achieved in celiac patients.

The prevalence of NCGS is at least six times higher than that observed in CD. Half of the NCGS patients have the genes encoding DQ2 or DQ8 molecules in their HLA system. The genes encoding DQ2 or DQ8 molecules are present in 95% of the CD patients. Negative re‐ sults for both HLA-DQ2 and HLA-DQ8 excluded the diagnosis of CD in at least 95%. These genes are present in healthy people as well (30%), but less frequently than in the case of the NCGS patients (50%).

The adaptative immune response may play a role in the NCGS pathogenesis. Contrary to CD, where the secondary immune response is upregulation, the NCGS patients demonstrate mainly upregulation of the primary response, and there is no increased expression of the genes of the secondary immune response including IL-6, IL-21, and IFN-gamma, which is characteristic of CD. The NCGS patients' gastrointestinal tracts and their intestinal permea‐ bility are normal, and the lesions in the histological picture of their duodenal mucosa are minor (Marsh 0 classification, in the majority of cases).

NCGS treatment is identical to CD and consists in the prescription of a gluten-free diet, which must be followed in a strict form during long life, avoiding all the crossed contamina‐ tions and also the possible unannounced interruptions of the diet.

Finally, I want to thank all the authors for their wonderful contributions, as well as the speed and efficiency in the delivery of their chapters. A special gratitude should be men‐ tioned to all the excellent team from the Editorial Board of InTech, especially to Ms. Marija‐ na Francetic, for their continued support and final condition of this book.

> **Prof. Luis Rodrigo, MD** Emeritus Professor of Medicine University of Oviedo Oviedo, Spain

**Section 1**

## **Celiac Disease**

symptoms, behavior disturbances, and systemic manifestations. In the medical literature, some other names have been suggested for this disorder, such as gluten sensitivity (GS),

This new entity was described around 30 years ago, but it was necessary to wait until 2011, when it was proposed by members of the First Expert Meeting on gluten sensitivity. The new defini‐ tion (the Oslo definition) of CD suggested that the disorder should be named NCGS, which made it distinguishable from CD. The Second Expert Meeting on GS that was held in Munich in 2012 decided to change the name of this disorder to NCGS in order to avoid confusion with CD. The first case reports of NCGS in children were described in 2012. NCGS can be diagnosed in those patients with gluten intolerance who do not develop antibodies that are typical neither of CD nor of wheat allergy (WA) and who do not suffer from lesions in the duodenal mucosa, which are characteristic of CD. The gluten-free diet leads to complete regression of symptoms in

The prevalence of NCGS is at least six times higher than that observed in CD. Half of the NCGS patients have the genes encoding DQ2 or DQ8 molecules in their HLA system. The genes encoding DQ2 or DQ8 molecules are present in 95% of the CD patients. Negative re‐ sults for both HLA-DQ2 and HLA-DQ8 excluded the diagnosis of CD in at least 95%. These genes are present in healthy people as well (30%), but less frequently than in the case of the

The adaptative immune response may play a role in the NCGS pathogenesis. Contrary to CD, where the secondary immune response is upregulation, the NCGS patients demonstrate mainly upregulation of the primary response, and there is no increased expression of the genes of the secondary immune response including IL-6, IL-21, and IFN-gamma, which is characteristic of CD. The NCGS patients' gastrointestinal tracts and their intestinal permea‐ bility are normal, and the lesions in the histological picture of their duodenal mucosa are

NCGS treatment is identical to CD and consists in the prescription of a gluten-free diet, which must be followed in a strict form during long life, avoiding all the crossed contamina‐

Finally, I want to thank all the authors for their wonderful contributions, as well as the speed and efficiency in the delivery of their chapters. A special gratitude should be men‐ tioned to all the excellent team from the Editorial Board of InTech, especially to Ms. Marija‐

**Prof. Luis Rodrigo, MD**

University of Oviedo

Oviedo, Spain

Emeritus Professor of Medicine

gluten hypersensitivity, or nonceliac gluten intolerance.

the same way and efficacy that is achieved in celiac patients.

minor (Marsh 0 classification, in the majority of cases).

tions and also the possible unannounced interruptions of the diet.

na Francetic, for their continued support and final condition of this book.

NCGS patients (50%).

VIII Preface
