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Celiac disease, the great imitator

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For so many years syphilis was known as the “great imitator” disease, due to its variety of symptoms, only to now be relegated to being the great imitator of neurological diseases. Shame, pain. Because celiac disease has taken on that title with the same lack of compassion it shows for those who suffer from the disease. None.

Because celiac disease is not a digestive problem with gluten. It is not like lactose intolerance. It is not that drinking a beer can give you diarrhea.

Celiac disease is a systemic, chronic disease with a strong genetic predisposition for specific alleles. It is a disease with a strong genetic and hereditary component, with multi-organ effects. The abnormal response to gluten by the immune system can generate autoimmune antibodies that damage any organ in the body. In fact, like most autoimmune diseases, it is 2-3 times more common in women than in men.

But why the nickname? Because the symptoms that people relate to celiac disease are more of an exception than a rule: malabsorption, diarrhea, malnutrition. Digestive problems are usually mild and/or intermittent, often accompanied by non-digestive symptoms that the affected person does not relate to celiac disease.

At the digestive level, the symptoms are actually a range of possibilities, sometimes opposite between patients, such as weight loss in some and obesity in others. Sometimes the patient seems asymptomatic because they have become accustomed to living in chronic poor conditions, taking them as the norm.

Outside the digestive system, we have: tiredness, headache, neurological disorders, bone weakness, oral, cutaneous problems, anemia, iron deficiency (low iron levels, which can cause anemia on their own), allergic processes… We could almost finish by listing the symptoms that celiac disease has never caused.

celiaquia

Imitator, genetic, chronic, and globally popular.

It is a disease that can appear at any age, with a prevalence of 1-2% of the world’s population.

“And is that a high prevalence, doctor?”

It is, it is. It is the most prevalent food-related disease in the West. In Europe, it is estimated that there are between 3.5 and 4.5 million celiacs. And it is believed that the majority of celiacs are not even diagnosed. It is estimated that 83% of those affected by this disease are unaware of it.

“And are those many patients not being properly informed?”

Oh my god, so many. Currently, this disease cannot be ruled out with a single test. This, coupled with the fact that even when there is a diagnosis, that person has spent years living with the pathology and going from doctor to doctor, including specialists, with the consequent cost in time and money.

In addition, it has a very universal and homogeneous distribution, so there are very few characteristics that help to narrow down the predisposition. A similar presence of the pathology has been described in almost all parts of the world.

Fortunately, the treatment is simple and accessible to everyone (in theory): follow a completely gluten-free diet for the rest of your life. I said simple, not pleasant. When you tell my dad he can’t eat bread anymore, he asks for euthanasia straight away. And the sooner the diet starts, the better, to recover the body from the damage caused during the period of gluten intake.

One problem is that parenthesis that says “in theory.” In practice, that diet is more complicated than doing intermittent fasting while working in a bakery. And not because people decide they feel good and want to try those new unicorn-shaped cereals with extra wheat, although there are people like that too. Those affected usually continue to ingest very low doses of gluten inadvertently, especially due to cross-contamination. There may be contaminations in the preparation of food or the consumption of products with gluten that the affected person is unaware of, such as some medications. Eating out is a risky sport for these people.

What causes this primordial genetic disease?

It’s quite ancient, as there are descriptions of the disease that date back 2,000 years. It’s a combination of three factors: genetic predisposition, gluten + additional factors, and the immune system response. The villain of the story is not actually gluten, but rather gliadins. Gliadins are the alcohol-soluble fraction of gluten, and they contain most of the toxic products.

These molecules are quite mischievous. For starters, they are resistant to degradation in the digestive system, so they arrive in the intestine at full capacity. Then, one of their capabilities is to increase the permeability of the intestine, making it easier for them to penetrate the intestinal barrier. Finally, they reach the submucosa and trigger an inflammatory process mediated by CD4+ lymphocytes. These are known as T helper cells, but here they are helping you die.

The innate immune system also participates in the process. Enterocytes, the epithelial cells of the intestine, release molecules that attract lymphocytes to the area. In severe cases, they are rewarded with death at the hands of NK cells. However, in most cases, the inflammation is mild and specific antibodies are not found in the blood, making it “invisible.”

In fact, the enormous variety of symptoms mentioned previously is caused by:

  • Damage to the intestine which makes it difficult to absorb essential nutrients, whose deficiency is reflected in failures in different organs and tissues.
  • Autoimmune activity.

Precisely, the immune system activity is used to try to make a diagnosis. By performing a blood test, antibodies against gluten that serve as serological markers are sought. The most frequent, due to its simplicity/speed/price relationship, is the anti-tissue transglutaminase type 2 antibody. However, its absence does not eliminate the possibility of the presence of the disease. Simply put, it is the best method to use first.

Other more comprehensive analyses are carried out, such as genetic markers for celiac disease and duodenal biopsies. Biopsies are the gold standard and most important test. Taking a piece of the upper part of the intestine gives a lot of information. Since this disease has decided that being complicated gives it immense pleasure, the damage to the tissue is not uniform, but rather patchy, so it is recommended to take several samples.

When everything fails, the final diagnostic technique is for the person to follow a gluten-free diet for 6-12 months. Over time, they are monitored, and if they improve, gluten was responsible for the damage.

Genes are just as responsible as gluten

Celiac disease is a condition where genetics play a strong role. We can see this in the fact that there is an 87% heritability, although the mode of inheritance is not well understood. To clear up any doubts: yes, celiac disease is considered a hereditary disease.

The most studied and related genes in celiac disease are the HLA-DQ2 and HLA-DQ8 haplotypes (a set of genes). The genes in the HLA system are usually inherited together and are responsible for recognizing and differentiating between self and foreign molecules. Without them, the immune response of the organism would be almost impossible. They are, for example, responsible for the rejection of transplants between different individuals. Each block of HLA genes, which usually come in a package, is a haplotype.

The HLA-DQ2 haplotype is found in 90% of celiacs. It should be noted that this is a case where A usually implies B, but not B usually implies A. Of all carriers of the HLA-DQ2 haplotype, only 2-5% are celiac.

The HLA-DQ8 haplotype is found in 5% of celiacs. Other genes and haplotypes of the HLA package have been associated with other immune system diseases, such as type I diabetes. The importance of both lies in their use, taking advantage of their high negative predictive value. It is very likely that a person who has the disease also has these specific haplotypes.

It has been calculated that having one of the two copies causes a 3% risk of developing the disease, and 10% if both copies are these alleles. Since HLA is a combination of genes, a person may have one of these haplotypes without their parents being carriers of them. And no mutations are required for this!

It is known that outside of HLA there are other genes involved in susceptibility. This has been demonstrated in comparative studies between twins and siblings with identical HLA.

For example, the IL2-IL21 region of the human genome, a region on chromosome 4 with genes involved in the immune system, may be involved in celiac disease. If we look at specific genes, candidates to participate in the pathology are the MYO9B, ICAM-1, or CTLA4 genes.

Unfortunately, as with any complex disease, studying genetic causes is difficult. However, using a tellmeGen DNA test is not complicated, and we guarantee that it will not cause autoimmune diseases or your money back.

 

Carlos Manuel Cuesta

Graduate in Biology. PhD in Biotechnology

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