Celiac disease

Celiac disease is probably the prototype of pathologies linked to hypersensitivity to cereals, which to date have not yet been elucidated. It is similarly supposed that in many patients some systemic diseases are due to regular ingestion of cereals.

During the past decade, evolution of scientific knowledge has revealed new concepts in pathophysiology and in the clinical approach to celiac disease.

There is a genetic predisposition for intolerance to gluten; this is associated with the HLA region of the short arm of chromosome 6 (Wahab et al., 2002).

The mechanism of this disease is probably an immune response to hypersensitivity to gluten proteins. Gluten is a mix of proteins, classified into two groups, prolamins and glutelins. The major immunogenic protein is gliadine, a prolamin. Antigliadin antibodies are usually found in immune complexes associated with systemic manifestations of this hypersensitivity.

Furthermore, a delayed hypersensitive cellular reaction against gluten is responsible for intestinal hyperpermeability with respect to gluten and other foods, which also leads to systemic manifestations.

The classical presentation of gluten enteropathy consists of chronic diarrhea, weight loss, iron deficiency and other symptoms of malnutrition. Based on histological lesions, the progress of gluten enteropathy can be subdivided into three stages:

– Marsh I lymphocytic enteritis
– Marsh II lymphocytic enteritis with crypt hyperplasia
– Marsh IIIA atrophy of intestinal villi: partial
– Marsh IIIB atrophy of intestinal villi: subtotal
– Marsh IIIC atrophy of intestinal villi: total

Therefore, the final stage of celiac disease consists of atrophy of intestinal villi (Marsh III), inflammatory infiltrates in the lamina propria and degeneration of the intestinal epithelium.

Gluten intolerance may be asymptomatic or may appear as an irritable colon with iron deficiency anemia. Most probably, the majority of patients with a gluten intolerance exhibit such limited symptomatology that the diagnosis is never made (Kelly et al., 1990). The diagnosis is rarely made until adulthood and the prevalence in industrialized countries varies between 1/200 and 1/300 (Wahab et al., 2002). Celiac disease is associated with auto-immune diseases, carcinomas and lymphomas of the gastrointestinal system. A high incidence of Type 1 diabetes, autoimmune thyroiditis, sarcoidosis, pulmonary fibrosis, encephalopathy, and cerebellar atrophy has been observed in celiac patients (Holmes, 2002). Intestinal lymphoma is one of the most serious complications and can manifest in the form of a sprue that fails to respond to a gluten-free diet and of an ulcerative jejunoileitis (Holmes, 2002; Wahab et al., 2002). Secondary hyperparathyroidism with a risk of osteoporosis is present in one quarter of celiac patients (Valdimarsson et al., 2000). Antibodies against food antigens can also show a cross-reaction with the host’s proteins and induce an autoimmune response.

Guidelines for measuring anti-food IgG antibodies
In the following cases, it would be useful to proceed to an early diagnosis of gluten intolerance by a quantitative measurement of IgG anti-gluten antibodies and by introducing a gluten-free diet:
– Non-specific digestive disorders
– Systemic symptoms of unknown etiology
– Family history of gluten intolerance

The goal of early diagnosis and dietary measures is to prevent the development of celiac disease and the complications associated with it, such as intestinal lymphoma, and to reduce mortality from celiac disease (Holmes et al., 1989; Corrao et al., 2001). Given the high incidence of this disease, gluten intolerance is a major public health problem and routine screening for gluten intolerance is discussed for children (2 years old) and adults over the age of 40, given the bimodal distribution as a function of age (Mulder et al., 2002).

Serological tests by indirect immunofluorescence for IgG/IgA antigliadin and antiendomysium antibodies have extremely high specificity. Meanwhile, sensitivity is low in the early stages of the disease, not more than 31% in the case of partial atrophy of intestinal villi (Marsh IIIA, Rostami et al., 1999).

The ImuPro 300 method based on the ELISA detection principle (see section: The role of ImuPro 300 and background principles) helps detect small concentrations of specific antibodies even in asymptomatic subjects. To confirm the serological diagnosis, a quantitative dose of IgG and IgA antigliadin, antiendomysium and anti-transglutaminase immune globulins by ELISA is recommended in all patients having a positive IgG-anti-gluten result.

Early diagnosis is even more important since the histological anomalies of the intestinal mucous membrane persist in 10% of celiacs despite a gluten-free diet (Selby et al., 1999). At some stage of the disease it must be concluded that lesions of the mucous membrane are irreversible or precancerous or that there exists other hypersensitivity besides gluten intolerance. That is why a complete anti-food immunological profile is recommended.

For the autoimmune manifestations possibly related to gluten intolerance, a diet free of gluten and other offensive foods can reduce the inflammatory and immune stimulus and can also favourably influence prognosis of the disease.