Characteristics of gluten related disorders

In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%.

Gluten-related disorders (GRDs) are characterized by abnormal immunological responsiveness to ingested gluten in genetically susceptible individuals. Gluten proteins are present in wheat, barley, and rye. GRDs are heterogeneous, reflecting their autoimmune, allergic, and non-autoimmune-allergic etiology.

The most common general symptoms of GRDs include bloating, abdominal pain, constipation, diarrhea, headache, tingling and numbness in hands and feet, fatigue and joint pain.

Celiac disease (CD), dermatitis herpetiformis (DH), gluten ataxia (GA), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS) are the five major GRDs that present with a wide range of clinical manifestations.

Celiac disease
Celiac disease (CD) is the most prominent autoimmune gluten-related disorder. The ingestion of gluten in genetically predisposed individuals carrying HLA type Ⅱ DQ2/DQ8 alleles can arouse a T-cell mediated immune reaction against tissue transglutaminase, an enzyme of the extracellular matrix, leading to mucosal damage and eventually to intestinal villous atrophy.

When celiac disease patients follow a gluten-free diet, the normal architecture of the intestinal villi is restored and the skin lesions heal.

Dermatitis herpetiformis
Dermatitis herpetiformis (DH), also known as Duhring disease, is the cutaneous counterpart of CD (“skin CD”).

Dermatitis Herpetiformis (DH) is a chronic, autoimmune, and recurrent cutaneous-intestinal disorder identified in genetically susceptible individuals, which is often associated with celiac disease. Anti tTG (anti-tissue transglutaminase) antibodies that are produced in response to gluten exposure can also recognize epidermal transglutaminase (ETG).

Gluten ataxia
Gluten ataxia (GA) is a form of cerebellar ataxia, affecting mainly Purkinje cells, and is caused by antibodies released when digesting gluten that mistakenly attacks part of the brain in individuals that are sensitive and genetically susceptible.

Wheat allergy
An IgE and non-IgE mediated immune response characterize wheat allergy (WA), resulting in an allergic reaction in some individuals upon contact, inhalation, or uptake of foods containing wheat but not necessarily other grains as barley or rye.

Wheat allergy is classified into occupational asthma (baker’s asthma) and rhinitis; food allergy (FA), affecting the skin, the gastrointestinal tract or the respiratory tract; wheatdependent exercise-induced anaphylaxis (WDEIA) and contact urticaria. Ingested wheat can cause IgEmediated wheat allergies in both children and adults.

Non-celiac gluten sensitivity
Non-celiac wheat/gluten sensitivity (NCWGS) makes people experience symptoms similar to CD and WA. However, patients with NCWGS do not have specific IgE against wheat proteins or IgA anti-TG2 autoantibodies.
Characteristics of gluten related disorders

Major types of gluten-related disorders

There are three major types of gluten-related disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Each is distinct, but all are related and manageable.

Gluten is the generic term used to define the storage proteins found in many cereals, such as wheat, spelt, rye and barley. Gluten proteins appear to be prolamins due to the significant amount of glutamine and proline amino acid residues present in their primary structure. In people with celiac disease, those proteins cause an inflammatory response which leads to intestinal damage.

Celiac disease is an autoimmune enteropathy caused by genetic and environmental factors, with an estimated worldwide prevalence of about 1%. Celiac disease has been known for more than 2,000 years and it was already in the middle of the 20th century that its relationship with gluten intake was established.

The disease triggered by the ingestion of gluten and related prolamins in genetically susceptible individuals and characterized by a variable combination of clinical manifestations, specific antibodies, HLA DQ2 and DQ8 haplotypes and enteropathy.

Celiac disease affects each person differently. Symptoms may occur in the digestive system, or in other parts of the body. One person might have diarrhea and abdominal pain, while another person may be irritable or depressed.

Celiac disease also can cause dermatitis herpetiformis. Dermatitis herpetiformis (DH) is a bumpy, itchy skin rash that’s common in people with celiac disease.

Allergy to wheat is represented by a food IgE-mediated allergy, which is most frequently based on the sensitization to wheat protein allergens. It has been shown that wheat ω5-gliadin is the main allergen of gluten, inducing wheat-dependent exercise-induced anaphylaxis.

Allergy to wheat is characterized by the presence of digestive, respiratory and/or cutaneous symptoms, triggered by exposure to wheat through mucous (digestive or respiratory) or skin.

A third disorder, called nonceliac gluten sensitivity (NCGS), characterized by distress after gluten consumption and in which neither celiac disease nor IgE-mediated allergy plays a role. Gluten ataxia (GA) is one of a number of different neurological manifestations attributed to celiac disease, but there is also suggestion that it is related to NCGS.

Gluten ataxia is a rare neurological autoimmune condition involving human body's reaction to the gluten protein found in wheat, barley, and rye, can irreversibly damage the part of the brain called the cerebellum.

Non-celiac gluten sensitivity (NCGS), also referred to as non-celiac wheat sensitivity (NCWS), is a clinical syndrome characterized by both intestinal and extra-intestinal symptoms responsive to the withdrawal of gluten containing food from the diet.

Several epidemiologic studies have suggested that non-celiac gluten sensitivity NCGS may affect a variable range (from 0.5% to 13%) of the Western population. Currently, NCGS is a syndrome characterized by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food, in subjects in whom either celiac disease or wheat allergy previously has been ruled out.
Major types of gluten-related disorders

Symptoms of celiac disease

Celiac disease is the world’s most common genetic autoimmune disorder which affects the digestive process of the small intestine.

Celiac disease afflicts an estimated 1 in every 3,000 individuals in US. When a person who has celiac disease consumes gluten, a protein found in wheat, oats, rye and barley, the individual’s immune system responds by attacking the small intestine and inhibiting the absorption of important nutrients into the body.

Studies show that any people with celiac disease continue to et gluten, either by choice or unknowingly. Classical celiac disease can occur in adults but more typically begins in early childhood. It is characterized by symptoms that arise from damaged the small intestine.

The affected person has bloating and discomfort and diarrhea. Also, because the damaged bowel becomes unable to properly absorb nutrients in the body, the individual with classical celiac disease starts to break of his or her own some tissues to provide nutrients to supply energy for the body’s normal functioning.

Sometimes, people have celiac disease but don’t experience gastrointestinal symptoms. Nowadays doctors know that many people with celiac disease have symptoms in part of the body other than intestines; they many have no or only mild gastrointestinal symptoms.

These atypical symptoms are often caused by the lack of one or more nutrients due to the malabsorption of food resulting from damage to the small intestines.

Research has demonstrated that a significant percentage of children and adults with positive blood tests had no, or minimal, symptoms when they were tested.
Symptoms of celiac disease

What is celiac disease?

Celiac disease also known as celiac sprue, non-tropical sprue, and gluten-sensitive enteropathy, is a condition in which consuming gluten a protein found in wheat, rye, barley and some other grains.

Celiac disease is an autoimmune disorder. When human eat these grains, immune system responds by causing inflammation and damaging the small intestine.

What is gluten? Technically gluten is made up of the proteins glutenin and alpha gliadin, a specific type of prolamins in wheat. However, gluten has become a general term for any kind of potentially harmful prolamins.

Prolamins are the proteins in wheat, barley and rye that are harmful to persons with celiac disease. Wheat, rye, and barley prolamins are called gliadin, secalin and hordein, respectively.

The typical form of celiac disease presents with gastrointestinal symptoms typically between 6 and 24 months of age.

Symptoms begin at various time intervals after the introduction of gluten in the diet, also depending on its amount and on other environmental factors.

The key to successfully managing celiac disease is the complete elimination of gluten from the diet.
What is celiac disease?

Oat and celiac disease

Celiac disease is an inherited trait: however its inheritance is complex and poorly understood.

The intestinal damage that occurs in celiac disease is associated with the abnormal immunological response and intolerance to certain protein fractions of cereals. Individual with celiac disease have a sensitivity to prolamin fractions of wheat (gliadin), rye (secalin) and barley (hordein).

The only treatment for celiac disease is a strict gluten free diet for life. Previously, oats were also included in the list of cereals causing symptoms in celiac patients.

Celiac disease is characterized by diarrhea, emaciation, aphthous stomatitis malabsorption.

Finnish celiac disease and dermatitis herpetiformis patients had been using oat-containing gluten-free diets since 1997 (Peraaho M. Oats can diversify a gluten-free diet in celiac disease and dermatitis herpetiformis. J Am Diet Assoc 104(7):1148-1150).

The researchers found that 1000 randomly selected members of the Celiac Society, 73% with celiac disease and 55% with dermatitis herpetiformis.

Since 1995, several additional studies published found no adverse effects associated with the regular consumption of moderate amounts of oats. These studies have shown that oats suitable for both adult and child patients.
Oats and celiac disease

Gluten Sensitivity Celiac Disease

Celiac disease is a gluten sensitive enteropathy of autoimmune origin, characterized by inflammation and villous atrophy of the small bowel mucosa, that impairs nutrient absorption.

Celiac disease is also known as celiac sprue, nontropical sprue and gluten-sensitive enteropathy. Individual with celiac disease do not tolerate gluten, a protein present in wheat, rye, barley and possible oats.

The normal small bowel mucosa a is thrown up in a series of concertina-like folds called the valvulae conniventes. The absorptive surface of the mucosa is configured as millions of villi covered by columnar epithelial cells.

In advanced celiac disease, the valvulae are thinner and more widely spaced than normal. The damage may be restricted to the duodenum or may involve the full length of the small intestine.

Individuals with severe disease may malabsorp all nutrients to some degree, especially the macronutrients, fat-soluble vitamins, electrolytes, calcium, magnesium, zinc, iron, folate and vitamin B12.

As a result of nutrient deficiencies, patients often develop anemia and have low bone mineral density.

Other symptoms, such as severe abdominal pain, nausea and vomiting are much less common.

The diarrhea of celiac disease is classically describe as high volume, pale, loose to semi formed and foul smelling.

Celiac disease is one of the the most common chronic disorders in Europe and the US affecting about 1% of the population.
Gluten Sensitivity Celiac Disease