What is it?
Celiac disease is a permanent intolerance to gluten, to a mixture of proteins present in cereals such as oats, wheat, spelled, kamut, barley, rye, spelled and triticale.
In Italy it falls into the category of “social diseases”, as it is very widespread and affects one person every 100/150.
According to statistical data, the Caucasian race has a greater predisposition to the disease, compared to the Asian or African race, due to a greater consumption of cereals with gluten.
Celiac disease is classified into three forms, latent, silent and symptomatic celiac disease.
In latent celiac disease, patients possess anti-transglutaminase, antigliadin and anti-endomysus antibodies, but no damage to the villi that line the organ, with total absence of gastrointestinal symptoms. Nevertheless, a late diagnose or an incorrect diet can lead to damage to the intestinal mucosa over time.
In silent celiac disease patients test positive for specific antibodies to celiac disease, do not complain of any symptoms, but still experience villous atrophy damage to their small intestine.
In symptomatic celiac disease patients test positive for anti-transglutaminase, antigliadin and anti-endomysium antibodies and present inflamed intestinal mucosa and completely atrophied villi.
The causes of celiac disease are mainly genetic. Celiac patients are carriers of allelic variants predisposing the disease, 90% of them have the DQ2 haplotype, identifiable with the DQA1 * 0501 and DQB1 * 0201 genes, while the the remaining 10% have a DQ8 haplotype identifiable with the genes DQA1 * 0501 and DQB1 * 0202.
These genes encode proteins of the HLA complex, or proteins expressed on the surface of particular cells of the immune system, known as antigen presenting cells or APCs. The main function of these cells is to capture and process antigens for presentation to T-lymphocytes, and they produce signals required for the proliferation and differentiation of lymphocytes..
In celiac disease, patients with a DQ2 or DQ8 haplotype have APC cells that have a higher binding affinity for a protein fraction of gluten, known as gliadin. APC cells bind to gliadin and present it to the T cells of the immune system of the intestinal mucosa, triggering the inflammatory and chronic response.
The lymphocytes will recognize the gliadin as “foreign”, starting to secrete inflammatory cytokines such as IL-6, IL-8 and TNFα, which are mainly responsible for the damage of the intestinal mucosa.
The target organ of celiac disease is the intestine, so the main symptoms are mainly gastrointestinal and include:
- Swelling and abdominal pain;
- Blood in the stool
- Foul-smelling stools;
- Physical weakness;
- High transaminases;
- Bone and joint pain;
- Absence of menstruation in women;
- Herpetiform dermatitis;
- Aphthous stomatitis.
In children, the main symptoms are alternating diarrhea and constipation, abdominal cramps, dysentery, dehydration, marked abdominal distension, dyselectroliteemia, hypotension and lethargy. Other symptoms can be weight loss, delayed puberty, alopecia, stomatitis, mouth ulcers, chronic dehydration, dental enamel defects, neurological disorders such as slow learning, dyslexia, dysorthography, migraine, epilepsy , attention deficit, osteomyelitis, that is, fragility and inflammation of the bones.
A visual diagnosis of celiac disease is difficult to make, as its symptoms are similar to those of other diseases, such as irritable bowel, iron deficiency anemia, intestinal inflammation, diverticulitis, chronic fatigue syndrome.
For this reason, in order to have a certain diagnosis of celiac disease, it is advisable to carry out more specific and targeted clinical investigations.
The main clinical tests prescribed to diagnose celiac disease are:
- Blood test for the detection of anti-endomysium, antigliadin and anti-transglutaminase antibodies;
- Intestinal biopsy, to analyze the degree of inflammation of the intestinal mucosa;
- Genetic screening, to evaluate the presence of allelic variants predisposing celiac disease.
Currently the only therapy for coeliac disease is a strict lifelong gluten-free diet.
Researchers around the world are working to develop new treatments for celiac disease. Over the years the goal of research studies has been to find a vaccine that can create “tolerance” to gluten in celiac patients.
Dr. Robert Anderson of ImmusanT a Cambridge, Massachusetts, based biotech company was established to advance this knowledge into clinical trials.. The aim of this drug is to restore immune tolerance to gluten using peptide-based immunotherapy to induce T cells to make a regulatory response.
The vaccine has the scientific name of Nexvax2, consisting of three large peptides of a synthetic nature, which contain five of the gluten fragments, responsible for the activation of T lymphocytes.
These three peptides have been joined together, in such a way as to create a “combopeptide” which, dissolved in a physiological solution, is injected subcutaneously. The vaccine in question was tested on mice genetically predisposed to celiac disease. Following subcutaneous administration, it reduced the degree of inflammation in the intestinal mucosa. The reduction of inflammation affecting the intestinal mucosa is due to the fact that the vaccine stimulates the T cells of the immune system, residing in the intestinal mucosa, to secrete IL-10, an anti-inflammatory cytokine .
Following the positive results in mice, the vaccine was tested on a group of celiac patients in Australia, giving very positive results, both in terms of toxicity and anti-inflammatory action.
The point is that a therapy can be considered efficient only if it can cure the majority of patients with celiac disease, allowing the total reintroduction of gluten, without any side effects.
In the case of celiac disease, the point is to understand whether the 3 peptides, used for the design of the vaccine, are immunostimulants for all celiac patients, or they can vary and depend on the different genetic or environmental background, such as the consumption of different varieties of toxic wheat and grains, or from the age at which intolerance is diagnosed.
We can conclude by saying that, today we do not have certain confirmation of the validity of the vaccine for celiac disease.
In the past vaccines composed of “combopeptides” have already been made for other forms of allergies such as cat hair or dog or mites. This does not guarantee the absolute validity of the gluten vaccine, but it can represent a starting point towards the discovery of a definitive therapy.
In recent times, research aims at specific treatments, with the aim of digesting gluten during leavening , through an enzymatic process, thus making the flours harmless.
The following studies show that the treatment of doughs during leavening, with lactobacilli, equipped with particular proteolytic enzymes, can reduce the gluten concentration below 10 parts per million, that is the threshold triggering the immune-inflammatory response. In the following study, 13 celiac subjects were monitored for 60 days, with 200 grams of wheat treated during leavening with lactobacilli, at the end of the following period, the sample patients did not show changes in the specific antibodies for celiac in the blood or worsening of the mucosa.
However, further studies have shown that the treatment of gluten with a bacterial trans-glutaminase of Streptoverticillium reduces its immunotoxicity. As gluten treated with the following enzyme is not recognized by the immune system, thus reducing the inflammatory response in the intestinal mucosa.
Not only that, but gluten treated with transglutaminase does not create digestive alterations or complications for humans, it would seem over time to reduce the immune and inflammatory response to gluten following re-exposure and finally in the kidney the products treated with transglutaminase, are metabolized and eliminated without any problem.
As previously mentioned, the only therapy present as a cure for celiac disease is the permanent elimination of gluten from the diet. If we can say so, the positive aspect of this pathology is that once gluten is excluded from the diet, the intestinal mucosa is able to regenerate and eliminate the state of chronic inflammation, and in this way the patient will not show any specific symptoms.
Furthermore, the diet of a celiac patient must be perfectly studied and targeted, with the integration of only cereals notified by the ministry of health, alternating with other forms of cereals, naturally gluten-free, such as rice grains, corn grains, buckwheat, amaranth, cassava, millet, quinoa, sorghum and teff.
In addition to a whole series of behavioral rules to be followed and respected with extreme attention:
- Wash your hands thoroughly whenever you touch foods that contain gluten;
- Reserve a separate room for the preparation of “celiac dishes”, in order to avoid all types of contamination;
- Kitchen equipment (such as pans, grills, fryers …), utensils (such as ladles, can openers, colanders …) must be washed carefully, if they have been in contact with gluten, or they must be used exclusively.