Using bioinformatics to mine allergen databases and epidemiological studies, investigators at NIAID have uncovered new information on what makes people allergic to allergens. The NIAID team found that the differences between the structure of foreign proteins and the structure of self-proteins made the foreign ones allergenic. The results of their work appear online in the July 18th issue of PLoS ONE.
Allergic diseases, such as asthma, food allergy, and seasonal allergies, affect millions of people in the United States and seem to be on the rise. Allergens, the substances that cause allergic reactions, can come from a variety of sources, including foods, grasses and weeds, pets, and pests. Certain proteins found in allergy-causing substances interact with the immune system to induce a response; however, what makes these proteins allergenic is unknown.
One popular hypothesis is that the more similar an environmental protein is to a protein found in microbes or people, the more likely it will be allergenic. By this rationale, people have allergies to pet dander because the genetic structure of the pet proteins is similar to the genetic structure of proteins found in people.
The NIAID team led by postdoctoral fellow Helton Santiago, M.D., Ph.D., and Thomas Nutman, M.D., chief of the Helminth Immunology Clinical Parasitology Sections in the NIAID Laboratory of Parasitic Diseases, set out to prove this hypothesis, but found something very different.
The team searched a database of 499 known allergens to find similarities between the genes of allergens and the genes of parasitic worms and protozoans, bacteria, and fungi. They found that 312 allergens were significantly similar to genes found in worms, protozoa, or fungi, and that 180 of these allergens were similar among all three groups of microbes.
The researchers then examined data from epidemiological studies of allergies in people to determine how strongly each allergen elicited production of immunoglobulin E (IgE), the major antibody involved in allergic reactions. They found that in general allergens that are structurally dissimilar to microbes induced more IgE than allergens with structures similar to microbes.
Next, the team compared the genes of the allergens to the human genome. They came to the same conclusion: the major allergens that induced a strong IgE response in the population, such as major dust mite allergens, had relatively low structural similarity to human proteins.
These findings suggest that differences in structure between a foreign protein and its human counterpart determine whether or not it is allergenic. Like antigens (molecules found on disease-causing microbes that elicit an immune response), the more an allergen differs in structure from a self-protein, the more allergenic it is. Potentially, known allergens could be modified to make them structurally different and then used in therapeutics to treat allergic diseases, but much more research needs to be done.
The next step for this work is to first demonstrate the findings in animal models of allergy and then to confirm these results in studies in people with allergies.
Santiago H, Bennuru S, Ribeiro JMCR, Nutman, TB. Structural differences between human proteins and aero- and microbial allergens define allergenicity. PLoS ONE. July 18, 2012 (online ahead of print).