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02 March 2017


A new link has been reported between coeliac disease and a high-grade form of lymphoma.

Some people with coeliac disease develop a severe complication called refractory coeliac disease type II. This raises the number of lymphocytes lacking B-, T-, and natural killer-cell lineage markers in the duodenum.

For about half of patients with this condition, these abnormal lymphocytes lead to a lymphoma for which no effective treatment is available.

Dr Jeroen van Bergen of Leiden University Medical Centre, the Netherlands, and colleagues outlined this process in The Proceedings of the National Academy of Sciences. They say it probably involves cells called gluten-specific CD4+ T cells.

Their tests show that these cells, taken from duodenum samples, 'produce cytokines able to trigger proliferation of malignant lymphocytes.' They add that small-molecule inhibitors targeting the JAK/STAT pathway and the PI3K/Akt/mTOR pathway can block this proliferation.

'These data provide evidence implicating CD4+ T-cell cytokines in the pathogenesis of refractory coeliac disease type II. More broadly, they suggest that adaptive immune responses can contribute to innate lymphocyte activation during mucosal inflammation.'

Dr van Bergen explains: 'The immune system is seen as an ally in the battle against cancer, but that isn't always the case. 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.'

Dr Lara Bennett of the Worldwide Cancer Research commented: '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.'

Source: Kooy-Winkelaar, Y. M. C. et al. : CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes. PNAS 3 January 2017; doi: 10.1073/pnas.1620036114


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