Pathogenesis of Celiac disease

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Article written by MSc.Dr. Mai Vien Phuong - Department of Medical Examination & Internal Medicine - Vinmec Central Park International General Hospital
Celiac disease is also known as gluten sensitivity or gluten intolerance. This is an allergy to a form of protein called gluten, which does not allow the body to absorb gluten.

1. What is Celiac Disease (Gluten Intolerance)?

Gluten is found in many flours and grains, such as barley, wheat, and oats. This allergic disease affects mainly the small intestine, where food is stored after leaving the stomach.

2. What are the signs and symptoms of Celiac disease?

Common symptoms of Celiac disease include: diarrhea, accompanied by gray or liquid stools, often foul-smelling, oily and foamy looking; weight loss; growth and development delay (in young children); frequent bloating; abdominal swelling or pain; mouth sores; tired; weak people; Haggard; rash or muscle cramps.
Adults with Celiac disease often have fewer symptoms than children, so your doctor will diagnose it with a blood test to detect abnormal anemia. Another rare manifestation of Celiac disease is herpes.
You may experience other symptoms and signs not mentioned. If you have any questions about the signs of illness, consult your doctor.

3. Complications of Celiac Disease

Complications of celiac disease include treatment-resistant, collagenous ulcers, and intestinal lymphoma. Intestinal lymphoma affects 6 to 8% of patients with celiac disease, often manifesting 20 to 40 years after the disease. Rates of other gastrointestinal cancers (eg, esophageal or oropharyngeal carcinoma, small bowel carcinoma) are also increased. Adhering to a gluten-free diet can significantly reduce cancer risk.
If people who have been doing well on the gluten-free diet for a long time, are found to have symptoms of celiac disease, doctors often do a colonoscopy with a small bowel biopsy to check for signs of celiac disease. intestinal lymphoma.

4. Causes of Celiac Disease

Gluten plays an important role in the pathogenesis of Celiac. Gluten is the prolamin (plant protein) in grains including giadin in wheat, Sealin in rye, hordein in barley.
These are peptide chains rich in proline and glutamine, so they are difficult to break down by gastric acid, pancreatic enzymes or intestinal enzymes, even in healthy people. In normal humans, the epithelial layer of the intestinal mucosa does not allow passage of the wheat-derived gliadio peptide chains. Celiac is a chronic autoimmune disease caused by exposure to gluten in the lining of the digestive tract. In this pathology, the physiological protective barrier of intestinal epithelial cells is disrupted because the giadin chains pass through the epithelial layer, activating a variety of immune mechanisms that damage the intestinal epithelial cells.

5. Pathogenesis of Celiac disease?

In the medical literature, cases describing symptoms such as Celiac have been mentioned for a long time, but gluten was only identified as a major initiating factor in the disease after a Dutch doctor observed the symptoms of celiac disease. Celiac babies improved during the 1944-1945 famine, when wheat and barley became scarce.
Since then, many studies have been conducted to confirm that the pathogenesis of this pathology is the interaction between genetic, environmental and immune factors
5.1 Genetic factors Weak Genetic factors play an important role in this disease. These epidemiological studies have shown that up to 20% of Celiac patients have a parent or sibling with the disease. The rate of co-infection in identical twins is 75-80%, fraternal twins is 10%.
The genes identified to be involved in the disease are also the genes associated with human leukocyte antigen (HLA) or the major histocompatibility complex (MHC) group II.

The HLA genes are located on chromosome 6 and are divided into three groups (I-III) in which HLA-DQ belongs to group II located at position 6p21 responsible for the presentation of peptides from outside the cell. HLA - DQ consists of two chains a and two sequences regulated by genes HLA- DQA1 and HLA-DQB1 respectively, for example DQ2.5 is a protein encoded by genes DQB102 and DOA105. These peptides are located at receptors on the surface of antigen-presenting cells. The two most important genetic factors identified in Celiac are HLA-DQ2 and HLA-DQ8. The highest risk factor group is the two autosomes carrying DQB1*02 with the prevalence in the community is 2% and the prevalence in Celiac patients is 25%. Celiac patients carrying both alleles tend to have earlier disease onset, more complex course, and higher rates of treatment resistance. The heterozygous form DQ2.5 (DQB1*02/DQA1*05) is the most common form, accounting for about 50% of Celiac patients. With DQ8, two strings a. encrypted by DQA1*03:01 and two strings of 8 encoded by DQB1*03:02. The rate of HLA-DQ8 gene carrier in Celiac patients is about 5-10%, mainly in many Middle Eastern and South American countries. The percentage of patients with Celiac who do not carry both HLA-DQ2 and HLA-DQ8 is very low. According to a large European study of 1008 Celiac patients, only 4 cases did not carry any alleles of these two genes.

5.2 Environmental factors 5.2.1 Gluten Wheat, barley, and rye belong to the plant group Triticeae which is different from oats which belong to the group Avenaeae. “Gluten” is a general term for the plant proteins that trigger the occurrence of celiac disease including gliadin, glutenin in wheat and hordein, secalin in barley.
Avenin (oat peptide) rarely triggers immune dysfunction in Celiac. Gluten has a high content of proline and glutamine and is difficult to be broken down by gastric acid, pancreatic enzymes, and intestinal enzymes.
These undigested peptide fragments cross the epithelial barrier in the small intestine to reach the subepithelial connective tissue layer, thereby activating a series of immune responses. This process has the role of altering the permeability of intestinal membranes and peptide fragments are transported mainly by transmembrane mechanisms.

5.2.2 Intestinal microbiota The interplay between gut microbiota, diet and the immune system plays a role in the pathogenesis of obesity, chronic inflammatory bowel diseases and is currently under investigation. study in Celiac.
Studies using fecal specimens or biopsies of the intestinal mucosa showed differences in the distribution of Bacteroides, Clostridium, Bifidobacteria, Lactobacillus, Escheherria coli and Staphylococuss strains in Celiac patients compared with normal subjects. often.
A study in children with Celiac transition from tolerance to immune response noted a decrease in Bacteroidetes and a spike in Firmicutes. Experimental animal studies also confirm that the gut microbiota can alter cell membrane permeability, thereby contributing to the pathogenesis of Celiac.

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