Celiac disease (celiac disease): the cause

The cause of the development of gluten enteropathy (celiac disease) is congenital deficiency or decreased production of the small intestine enzyme that breaks down gluten. Gluten is found in cereals - wheat, rye, barley, oats.

Gluten intolerance is inherited and occurs in 0.03% of the population. In 80% of patients, histocompatibility antigens HLA-B8 and HLA-DW3 are detected, which are transmitted on a recessive basis.

Hereditary intolerance to gluten occurs in 0.03% of cases of the general population. Its frequency varies from country to country. Most often (1: 300) occurs in Western Ireland. According to research, gluten intolerance among adults in the middle of our country is quite rare.

Pathogenesis of celiac disease

Three hypotheses are expressed regarding the mechanism of the damaging effect of gluten:

1. gluten enteropathy arises from immunological reaction to food gluten;
2. genetic factors facilitate the adverse effects of gluten;
3. gluten enteropathy is a disease associated with a metabolic disorder, in which as a result of incomplete digestion of gluten accumulation of toxic substances damaging the mucosa occurs.

The role of immune mechanisms in the pathogenesis of celiac disease is indicated by an increase in the content of immunoglobulins and lymphocytes in the intestinal mucosa of the small intestine in patients with untreated gluten enteropathy. The mucous membrane of these patients synthesizes significantly more IgA and IgM than those in the control group whose biopsies have been treated with gluten in vitro. Sometimes only serum IgA levels increase, although cases of gluten enteropathy with selective IgA deficiency are described. In gluten enteropathy, among the mucosal-synthesized small intestine of immunoglobulins, the percentage of antiglutenic specificity is high. This makes it possible to assume that the gut affects the action of gluten by the production of anti-gluten antibodies. In the serum of many patients, circulating antibodies to gluten fractions are detected. Some authors consider their appearance as a nonspecific reaction to the passage of incompletely split gluten products through the permeable intestinal epithelium and as a peculiar cellular hypersensitivity to gluten. It is believed that gluten is activated by the "endogenous effector mechanism", which contributes to its local toxic effect in gluten enteropathy.

Changes in cellular immunity may play a role in the pathogenesis of celiac disease. This is evidenced by a marked increase in the number of T-lymphocytes in its own layer of the small intestinal mucosa and among inter-epithelial lymphocytes, the number of which is significantly increased in untreated celiac disease, including in the mucosa of the rectum. It is believed that sensitized T lymphocytes produce lyfokines in response to gluten, which contribute to mucosal damage.

The possibility of participation of corticosteroid hormones in the pathogenesis of the disease is discussed. The addition of hydrocortisone to the tissue culture of the ejaculatory mucosa of patients with untreated gluten enteropathy can suppress the harmful effects of gluten on tissues. Clinical and morphological improvement under the action of corticosteroids is associated with nonspecific suppression of inflammation and influence on secondary adrenal insufficiency. A number of authors consider celiac disease as a kind of allergic or infectious (adenovirus) lesion of the intestine.

There is no doubt a role in the development of celiac disease and genetic factors. This is evidenced by a much larger number of cases in relatives of patients compared with control populations. In one family, 4 cases of gluten enteropathy, confirmed with biopsy, and 11 sick relatives among 96 examined from 17 families were described.

Symptoms of celiac disease in sick relatives were either absent, or were so insignificant that they were not regarded as abnormalities. Approximately 10% of the first generation of relatives were dominated by the latent course of gluten enteropathy, which occurs more often than is diagnosed. In 80% of patients, the histocompatibility antigen HLA-B8 and HLA-DW3, often associated with the antigen HLA-B8, were found. However, not all HLA-B8 and / or DW3 carriers develop gluten enteropathy, nor do all of the patients in this disease detect one or both of the indicated HLA antigens. Antigenic disorders are inherited by a recessive type.

The emergence of celiac disease is also caused by metabolic disorders as a result of accumulation of toxic products in the mucosa of the small intestine due to incomplete splitting of gluten. At the same time, the content of some specific peptidases (aminopeptidase), involved in the digestion of gluten, is reduced. After successful therapy, the level of these peptidases in the histologically normal mucosa returns to normal.

Products deficient in the breakdown of gluten, in particular its water-soluble fraction, in contact with the mucosa of the small intestine, damage it, which is crucial in the pathogenesis of the disease. Low molecular weight acidic polypeptides also have a toxic effect. Above all, the absorptive cells of the small intestinal mucosa are affected, the rest of its layers are usually not involved in the pathological process. This lesion can be different in severity and extent, which explains the variety of clinical manifestations of the disease - from asymptomatic course to the development of severe insufficiency syndrome.

The morphological substrate of celiac disease is the defeat and decrease in the number of absorptive cells, the flattening or disappearance of villi, a significant increase in the number of proliferating undifferentiated crypt cells, a marked lengthening of crypts, an acceleration compared to the rate of cellular renewal and migration.

Thus, the development of celiac disease is due to the following pathogenetic mechanisms:

• Accumulation of toxic substances damaging the mucosa of the small intestine

Due to the deficiency of specific enzymes, in particular aminopeptidases, there is no complete cleavage of gluten in the intestine, which includes L-gliadin, which is a toxic substance. The products of insufficient splitting of gluten, low molecular acidic polypeptidases and, above all, L-gliadin have a toxic damaging effect on the small intestine. The mechanism of this action has not been fully studied.

• Development of immunological reactions to food gluten

In response to the entry of gluten into the lumen of the gluten, anti-gluten antibodies are produced, in the production of which the small intestine itself participates. Gluten binds to specific receptors of enterocytes and interacts with interepithelial lymphocytes and lymphocytes of the lamina propria of the small intestinal mucosa. The resulting antibodies interact with gluten, an immunological reaction develops with damage to the intestinal mucosa. In addition, sensitized T lymphocytes produce lymphokines in response to gluten, which exacerbate damage to the small intestinal mucosa.

As a result of the abovementioned pathogenetic factors, enterocyte damage occurs, atrophy of the small intestine mucosa with the disappearance of villi and crypt hyperplasia develops. There is also a marked infiltration of the surface and pit epithelium with lymphocytes, and the own plate with lymphocytes and plasmocytes. Atrophy of the mucous membrane leads to the development of severe malabsorption syndrome.

[1], [2], [3], [4], [5], [6], [7]