Researchers at National Jewish Health have found levels of the enzyme Pim 1 kinase increase in the small intestines of mice with peanut allergies.
Blocking activity of Pim 1 significantly lessened the allergic response to peanuts.
Previous research has told us that around four percent of Americans have a food allergy. Allergic reactions to food generally cause symptoms such as hives, vomiting, difficulty breathing, or most severely, anaphylaxis.
If a person with a peanut allergy consumes peanuts, the proteins enter the bloodstream via the intestines and cause a full-body immune response. A reaction can occur within minutes or hours of eating peanuts. First clues of a reaction can include: sneezing, tingling sensation on the lips, tongue, and throat, followed by a look of paleness, feeling sick, warm, or light-headed. People with asthma who also have a peanut allergy are more likely to develop life-threatening reactions. The cause of peanut allergies are not yet known.
Dr. Gelfand, senior author and chair of pediatrics at National Jewish Health says, "Pim 1, and its associated transcription factor, Runx3, play a crucial role in allergic reactions to peanuts. As such, they offer promising new targets for the treatment of allergic reactions to peanuts, and possibly other foods."
Pim 1 kinase contributes to several signaling pathways and is expressed in T cells and eosinophils, types of cells associated with allergic diseases. Runx3 is a transcription influence connected with the regulation of T cells.
The researchers used a mouse model of food allergy and discovered that Pim 1 kinase levels increased in the intestines of allergic mice that consumed peanuts, as well as other inflammatory cells and levels of cytokine molecules that are linked to allergies.
However, levels of Runx3 mRNA, decreased in the allergic mice. When the researchers issued a small molecule that blocks the activity of Pim 1 kinase, the mice did not experience diarrhea and other symptoms characterized by their peanut allergy.
A powerful cause of allergy symptoms, plasma levels of histamine, fell to about baseline levels after administration of AR460770, made by Array Biopharma. Eosinophils, inflammatory mast cells, and CD4 and CD8 T cells all rose only moderately, in reaction to peanuts.
Various cytokine signaling molecule levels associated with allergies, IL-13, IL-6, and IL-4, also fell after treatment with the Pim 1 blocker. Runx3 mRNA increased almost back to baseline levels.
Dr. Gelfand concludes:
"Our data identified for the first time that Pim1 kinase contributes in important ways to the development of peanut-induced allergic responses. Targeting this novel regulatory axis involving Pim 1 kinase and Runx3 offers new therapeutic opportunities for the control of food-induced allergic reactions."
Written by Kelly Fitzgerald