New Horizons in the Treatment of Celiac Disease

Celiac.com 06/10/2023 - If you suffer from celiac disease like I do you are well aware that the current and only treatment recommended for the disease is a lifelong adherence to a strict gluten-free diet. Anyone who has tried a gluten-free diet knows that it works fine as a treatment for the disease, but it also can be difficult to deal with, especially when cooking, dining out, and buying food (it can also be expensive!). According to one line of research done over the past few years, however, there may be hope that one day in the not too distant future we might be able to eat gluten without harm. How—you ask?

Immunotherapy

In 2001 the Scandinavian Journal of Immunology published an article authored by a group of Italian scientists wherein mice were used to test a new idea called immunomodulation and its ability to treat celiac disease. The scientists purified the protein gliadin (the component of gluten that triggers immune-mediated injury when ingested by people with celiac disease), fractionated it, and then administered the different fragments intra-nasally to laboratory mice (presumably transgenic mice with induced celiac disease, although this is unclear) and noted the results. They found that when a particular fragment of gliadin, which they refer to as alpha-gliadin, was administered intra-nasally it down-regulated T-cell proliferation and interferon-gamma production in response to whole gliadin in vitro. This lead the scientists to make the statement that "these results demonstrate how an immune response to a complex antigen may be controlled by treatment with a purified component and specifically indicate alpha-gliadin to be a good candidate for further identification of short peptides to be used as tolerogens in this model(1)."

Celiac.com Sponsor (A12):
Although immunomodulation sounds similar to allergy therapy it is not the same since the cells involved are different, as well as the method of induced tolerance. In therapy for allergic reactions tolerance is induced through injections, and the aim is to reduce histamine release, systemic anaphylactic responses, and even severe rhinitis. In immunomodulation the antigen in question is cleaved into smaller antigens, and the mixture of epitopes are used to induce tolerance via mucosal surfaces (i.e., the nose, parts of the respiratory tract, and the alimentary tract, to name a few). From my understanding, these are markedly different approaches, and the mucosal therapy appears to potentially be much more powerful and more selective in immune-suppression resulting ultimately in tolerance to the antigen. It is my hope that this research indicates a new avenue for the treatment of celiac disease, one which may be very soon in coming—possibly within the next decade. Of course, questions arise as to what exactly this particular experiment means, since findings were in vitro (i.e., test tube only, not within the body), were done on mice (murine studies), and do not seem to have been duplicated in humans at this point, suggesting difficulties / logistical problems with the protocol as it exists— using alpha-gliadin as a tolerogen to suppress immune response to dietary gliadin. Nonetheless, at the very least, this research signals that research advances are still being made into the understanding and treatment of celiac disease, and that better therapies and possibly even a cure for this disease may be on the horizon.

Reference:

1. Maurano F, Siciliano RA, De Giulio B, Luongo D, Mazzeo MF, Troncone R, Auricchio S, Rossi M. Intranasal administration of one alpha gliadin can downregulate the immune response to whole gliadin in mice. Scand J Immunol 2001 Mar;53(3): 290-5. Istituto di Scienze dell'Alimentazione, CNR, Via Roma 52, 83100 Avellino, Italy.