New Autoimmune Mutation Found in Enteritis Pathogenesis - European Medical Journal

New Autoimmune Mutation Found in Enteritis Pathogenesis

2 Mins

NOVEL immunotherapy has successfully ameliorated the symptoms of autoimmune enteritis following the discovery of a genetic mutation within an immune system protein.

Discovered in an adult patient, this genetic immunodeficiency and its consequent findings pose a number of interesting future research directions. Although there are >300 genetically determined immunodeficiencies currently known, the mutations themselves are relatively rare, are thus hard to detect, and are often discovered too late to be useful in treatment.

In this particular case, the protein CTLA-4, found on the surface of T cells, was found to have a mutation in its genetic expression. As a result, the affected protein allowed immune cells to attack the patient’s own intestinal cells, rather than suppress aberrant responses to protect the host cells, thus causing chronic inflammation and consequently severe diarrhoea. The mutation was traced using whole genome analysis, and further investigation demonstrated the reduced CTLA-4 function.

Following the detection of this novel genetic immunodeficiency, the researchers also successfully treated the patient using the new monoclonal antibody vedolizumab. This drug prevents immune cells from binding to intestinal receptors by blocking surface adhesion molecules on the T cell surface, directly where the mutated protein is located. This immunotherapy ceased the infiltration of T cells into the intestinal tissue and, after 3 months, had successfully treated the chronic diarrhoea in this patient.

While in this case, the mutation is the at the root of disease pathogenesis for this kind of autoimmune enteritis, its function can be beneficial to others, notably melanoma patients. Ipilimumab, used to treat these patients, reduces T cell inhibition, which in turn enables them to attack the malignant melanoma cancer cells. Autoimmune intestinal inflammation, a side effect of this therapy, is now all the more understood following the team’s genetic finding and thus melanoma patients may also benefit from further insight into the CTLA-4 mutation. Prof Mike Recher, Department of Biomedicine, University Hospital Basel, Basel, Switzerland, urged that: “In order to expand our knowledge in these areas, doctors in clinics and regional hospitals must be on the alert for unusual disease phenotypes and refer such patients to specialised university hospital clinics for further evaluation.”


Join our mailing list

To receive the EMJ updates straight to your inbox free of charge, please click the button below.
Join Now