Celiac disease is an autoimmune disorder triggered by the consumption of gluten. The disease affects a few million people in the United States, and new research shows how some of these people may even develop a rare form of cancer when they consume gluten.

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New research shows how the consumption of gluten may trigger a very rare form of lymphoma in a small group of celiac disease patients.

Celiac disease affects approximately 3 million U.S. adults, or roughly 1 percent of the healthy adult population in the country.

The disease is an inherited autoimmune condition. For people with celiac disease, the consumption of gluten – a protein found in cereal grains such as wheat, rye, and barley – causes their immune system to attack the small intestine.

If left untreated, celiac disease may lead to complications such as osteoporosis, infertility, some brain disorders, and even additional autoimmune conditions.

In some rare cases, undiagnosed or untreated celiac disease may also cause cancer. A team of researchers at the Leiden University Medical Center (LUMC) in the Netherlands has recently shown that the body’s immune cells triggered by the consumption of gluten in patients with celiac disease may also lead to a rare form of lymphoma.

The findings were published in the journal Proceedings of the National Academy of Sciences.

For a small number of people living with celiac disease, a gluten-free diet is not enough to stop the otherwise severe symptoms. These patients are classified as having refractory celiac disease (RCD), which usually affects between 2 and 5 percent of celiac disease patients.

In one type of RCD called RCDII, the white blood cells found in the wall of the small intestine divide and multiply in excessive numbers. In approximately half of the RCDII patients, these cells, called lymphocytes, go on to develop into a particularly rare form of lymphoma.

This rare and very aggressive form of white blood cell cancer is called enteropathy-associated T-cell lymphoma.

The body’s T cells – a type of immune cell that controls the body’s reaction to gluten, among other things – have a very strong inflammatory reaction to gluten. When they detect the protein they produce cytokines, which in turn stimulate other immune cells. This leads to the extremely inflammatory and painful response typical of celiac disease, but in some rare cases, it also leads to cancer.

Researchers have known that the onset of this rare form of lymphoma depends on the cytokine IL-15, which makes malignant cells multiply. In this latest research, however, scientists in the Netherlands have now shown that three other cytokines – TNF, IL-2, and IL-21 – can also cause malignant cell proliferation.

These findings serve to further clarify how the body’s immune system responds to gluten and how this can stimulate the growth of cancerous cells in RCDII.

Dr. Lara Bennett, science communications manager at Worldwide Cancer Research, comments on the significance of the findings:

This is another great example of the importance of early-stage, discovery research. This is a rare type of cancer but the findings could be of real benefit to this small but important group of patients with refractory coeliac disease.”

LUMC researcher and Worldwide Cancer Research scientist, Dr. Jeroen van Bergen, explains why the next important step in this research is identifying where exactly in the development of lymphoma these three cytokines get involved.

“It is likely that at the time of lymphoma diagnosis, the patient has already experienced decades of intestinal inflammation,” Dr. van Bergen says. “We need to determine the extent to which it would actually help to block these newly discovered growth factors with targeted drugs at the time of diagnosis. In the meantime, we have tested a large number of potential drugs in the laboratory, and two of them seem promising. But this is only interesting in terms of a new treatment if these growth factors still have a role to play in the growth and development of the lymphoma after diagnosis.”

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