New research shows gluten contributes to the development of a very rare, but deadly, blood cancer in a small group of celiac patients

The scientists at Leiden University Medical Center (LUMC) have shown that immune system cells, which react to gluten, produce chemicals called cytokines that can contribute to the development of a rare form of lymphoma (cancer of the white blood cells).

The findings were published in the Proceedings of the National Academy of Sciences (PNAS). LUMC researcher and Worldwide Cancer Research scientist, Dr Jeroen van Bergen, explained: "the immune system is seen as an ally in the battle against cancer, but that isn't always the case."

Refractory celiac disease

Celiac disease is an autoimmune disease where special immune system cells, called gluten-specific T cells, have an extraordinarily strong inflammatory reaction to gluten. The cells produce chemicals, called cytokines, which then stimulate other immune system cells.

Celiac patients control their symptoms by following a gluten-free diet. However, a small percentage (2-5%) of patients diagnosed in adulthood does not respond to such a diet, due to long term inflammation and damage, and have what is called refractory celiac disease (RCD).

In one type of refractory celiac disease, called RCDII, immature white blood cells from the immune system (called lymphocytes) which are located in the wall of the small intestine, multiply in number in an uncontrolled manner. In about half of the patients, these cells develop into a malignant, incurable form of white blood cell cancer called enteropathy-associated T-cell lymphoma (EATL), an exceptionally rare and aggressive type of lymphoma arising from the inflammation caused by the body's reaction to gluten.

Growth factors

Scientists know that the lymphoma cells are dependent on a cytokine called IL-15 which encourages cells to multiply. Here the researchers have shown that cell proliferation can be stimulated just as effectively by three other cytokines, TNF, IL-2 and IL-21. These three cytokines are produced by the gluten-specific T cells, in response to gluten. The new findings thus provide a potential mechanism by which the immune response to gluten contributes to the growth of malignant cells in RCDII and opens up new avenues of research.

Targeted treatments

An important question now is to find out at which stage of lymphoma development these cytokines are involved.

Dr van Bergen explained: "It is likely that at the time of lymphoma diagnosis, the patient has already experienced decades of intestinal inflammation. 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 as I said, 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."

Dr Lara Bennett, Science Communications Manager at Worldwide Cancer Research added "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 celiac disease."