Scientists Have Finally Identified Where Gluten Intolerance Begins

For roughly one in every hundred people, food containing even the smallest amounts of gluten can deliver a gutful of hurt.

While a domino effect of immunological reactions can be traced back to their genetic roots, a number of contributing factors are also involved, making it difficult to map the precise chain of events that causes an allergy to gluten to emerge.

Using transgenic mice, an international team led by scientists from McMaster University in Canada has identified a crucial role played by the very cells making up the gut's lining, describing a major stepping stone that could lead to new therapies.

Celiac disease is in essence an autoimmune disorder triggered by the presence of a group of structural proteins known as gluten in the intestines.

Eating virtually anything made with wheat, barley, or rye – meaning most baked goods, breads, and pastas – puts people with the condition at risk of bloating, pain, diarrhea, constipation, and sometimes reflux and vomiting.

Currently the only way to avoid the symptoms is to avoid the foods that trigger them.

"The only way we can treat celiac disease today is by fully eliminating gluten from the diet," says McMasters gastroenterologist Elena Verdu. "This is difficult to do, and experts agree that a gluten-free diet is insufficient."

Around 90 percent of people diagnosed with the condition carry a pair of genes that encode for a protein called HLA-DQ2.5. Of the remaining 10 percent, most have a similar protein called HLA-DQ8.

Like other kinds of 'HLA' (or human leukocyte antigen) proteins, the proteins hold pieces of fallen invaders aloft like macabre trophies on a class of immune cells, warning other defensive tissues to be on the lookout.

In the specific case of HLA-DQ2.5 and HLA-DQ8, the proteins are shaped to hold chunks of gluten peptide that are resistant to digestion, instructing murderous T cells to go on the hunt.

Unfortunately, these instructions aren't the clearest at distinguishing between a threat and similar-looking materials in our body, meaning those with the genes are at risk of a variety of autoimmune conditions.

Not everybody who expresses either HLA-DQ2.5 or HLA-DQ8 will develop an immune disorder like celiac disease, however. For that to happen, those torn-up pieces of gluten first need to be carried across the gut wall by a transporting enzyme that binds with the peptide and alters it in ways to make it even more recognizable.

Cells in the intestinal wall are responsible for releasing this transporting enzyme into the gut, so they clearly have a critical role in the early stages of the disease. They are also known to express the family of proteins to which HLA-DQ2.5 and HLA-DQ8 belong, which are typically regulated by inflammatory responses in the gut.

What hasn't been clear is how this staging ground for people with celiac disease actually functions within the pathology itself.

To focus on this important link in the chain, the research team double-checked the expression of the major immune complex in the cells lining the intestines of people with treated and untreated celiac disease, and in mice with the human genes for HLA-DQ2.5.

 

They then created functional living models of the gut, called an organoid, using the mouse intestinal cells in order to study the expression of their immune proteins up close, subjecting them to inflammatory triggers as well as predigested and intact gluten.

"This allowed us to narrow down the specific cause and effect and prove exactly whether and how the reaction takes place," says McMasters biomedical engineer Tohid Didar.

From this it became evident the cells lining the gut weren't just passive bystanders suffering collateral damage in a misguided effort to rid the body of gluten – they were key agents, presenting a mash-up of gluten fragments broken down by gut bacteria and transporting enzymes to gluten-specific immune cells first hand.

Knowing the types of tissue involved and their enhancement by the presence of inflammatory microbes gives researchers a new list of targets for future treatments, potentially allowing millions of people worldwide to enjoy a gluten-filled pastry or two without the risk of discomfort.

This research was published in Gastroenterology.

 

 

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Spring influenza in India: Doctors suggest how to avoid prolonged symptoms

Spring flu has gripped India causing a painful rasping cough for a longer period. According to a report by the Hindustan Times, the key reason behind the surge in flu cases is due to low immunity and the relative unpopularity of annual flu shots in the country. 

Dr GC Khilnani, former head of the pulmonary, critical care, and sleep medicine department at the All India Institute of Medical Sciences (AIIMS) told Hindustan Times that every other person is down with fever, loss of voice, and breathlessness.

“An uncontrollable cough, with or without wheezing, is a frequent symptom. The Influenza A virus (H3N2) is frequently diagnosed when tested," he told the daily.

The spike in flu cases in the country is similar to what the West experienced between September and January last year. The World Health Organization mentioned influenza A(H1N1)pdm09, A(H3N2), and influenza B viruses circulated in several countries.

A research paper--Household Transmission of Influenza A viruses in 2021-22 stated that "Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season".

Several doctors in India have said that they are witnessing cases of prolonged cough post-flu, including influenza, RSV (respiratory syncytial virus), adenovirus, rhinovirus, etc.

The probable reasons for prolonged cough could be pollution, new mutant pathogens reflux diseases (acidity), and irrational use of antibiotics, according to the doctors.

To combat respiratory infections, doctors have advised patients to wear masks and avoid crowded places.

"The vaccine against common flu is available and people must take it," the doctors told the daily.

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