Published Online: September 20, 2014
Celiac disease is an autoimmune disorder of the gastrointestinal tract characterized by an inflammatory response to dietary gluten, a major component of foods containing wheat, barley and rye. Strict compliance with a gluten-free diet is currently the only effective treatment for celiac disease, but the diet is inconvenient and expensive, and inadvertent gluten exposure is common. Parasitic worms such as hookworms are masters at regulating the immune system, thus several attempts have been made to exploit their immunosuppressive capabilities in clinical trials for various inflammatory disorders.
In an article recently published in The Journal of Allergy and Clinical Immunology (JACI), Croese, Giacomin, and colleagues show that experimental hookworm infection enables celiac disease patients to ingest escalating doses of gluten to the equivalent of a medium serving of pasta, with no deterioration in symptoms. Because gluten is predictably toxic for most people with celiac disease, historical control data were used to compare trial outcomes. Critically, in hookworm-infected subjects the architecture of the small intestine, inflammatory cell infiltration, and auto-antibody production did not display the typical pathologic responses associated with gluten ingestion when compared to pre-trial levels. Hookworm infection evoked multiple immunological changes in the intestine, where inflammatory cells that typify active celiac disease (interferon-gamma and interleukin-17-producing T cells) were suppressed, and anti-inflammatory cell types were expanded.
Using a novel, combined immunotherapy approach involving experimental hookworm infection and gradual re-introduction of small amounts of dietary gluten, the authors demonstrate a clear improvement in gluten tolerance in a cohort of people with celiac disease. Numerous objective and subjective outcomes were measured, with all results indicating a dramatic shift towards immune regulation at the expense of inflammation, translating into a clinical benefit and highlighting the therapeutic utility of parasitic worms, or worm-derived factors, for treating a range of autoimmune and allergic diseases.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.