A recent Science Translational Medicine study reports that food-specific immunoglobulin A (IgA) present in the human gut does not provide protection against food allergies.
Study: Food-specific immunoglobulin A does not correlate with natural tolerance to peanut or egg allergens. Image Credit: OMfotovideocontent / Shutterstock.com
Food allergies, a leading public health problem worldwide, are caused by the abnormal production of IgE antibodies against food antigens. The ingestion of certain food products leads to the IgE-mediated release of histamine, which subsequently initiates a cascade of allergic symptoms, including rashes, swelling, vomiting, diarrhea, respiratory and cardiovascular complications, and, rarely, fatal anaphylaxis.
IgA comprises 80% of the antibodies present within the human gastrointestinal (GI) system and is vital in regulating gut microbiota composition. In addition, the research suggests that food-specific IgA antibodies bind to and neutralize food allergens, thus leading to the development of food tolerance. However, this hypothesis is based on indirect and mixed evidence.
In the current study, scientists characterize food-specific IgA responses in infants and determine whether food-specific gut and plasma IgA antibodies protect against food allergens.
Peanut-specific IgA response
Fecal samples collected from 51 non-food allergic infants were analyzed for peanut-specific IgA antibodies. Fecal IgA is regarded as a relevant proxy for gut IgA.
Non-food allergic infants were found to produce detectable peanut-specific IgA in the gut. Further analysis revealed that these IgA antibodies might be derived from both the mother and child.
The researchers also measured peanut-specific gut IgA in 512 allergen-sensitive, non–peanut-allergic infants with a milk and/or egg allergy or eczema with milk sensitization and/or egg sensitization. These allergen-sensitive infants produced their own peanut-specific gut IgA antibodies. The presence of gut IgA antibodies was not associated with breastfeeding status or oral peanut exposure.
Protective role of peanut-specific IgA antibodies
Infants without a clinical history of a peanut allergy were enrolled in the current study to examine the presence of peanut-specific IgA antibodies in the gut and plasma. During the two-year follow-up period of these unsensitized children, no significant association of peanut-specific gut IgA at baseline was observed with peanut-specific IgE and clinical allergy outcomes at follow-up.
Similarly, peanut-specific plasma IgA at baseline did not correlate with peanut-specific IgE and clinical allergy at follow-up. These observations indicate that peanut-specific gut and plasma IgA do not provide any protection against a future peanut allergy.
Further analysis revealed that infants with a peanut allergy have comparatively higher levels of peanut-specific plasma IgA at baseline. Moreover, a positive correlation was observed between peanut-specific plasma IgE and peanut-specific plasma and gut IgA in these infants.
A separate set of analyses involving children with and without a peanut allergy indicated that peanut-specific plasma IgA is associated with peanut-specific plasma IgE and peanut allergy. However, no such correlation was observed for peanut-specific gut IgA.
Moreover, it was observed that peanut-specific gut IgA targets different epitopes than peanut-specific plasma IgE. Furthermore, peanut-specific gut IgA targets similar peanut epitopes, regardless of peanut allergy status.
Egg white-specific IgA response
Besides the peanut allergen, the gut IgA response to the egg white allergen was also assessed. Similar to peanut allergen, no significant difference in egg white-specific gut IgA levels was observed between children with and without an egg allergy.
Further analysis revealed that a higher level of egg white-specific gut IgA is not a marker of egg tolerance or outgrowth of an egg allergy.
The current study reveals that food-specific IgA is not a marker of clinical allergy or food tolerance. Both children with and without a food allergy produce detectable levels of food-specific gut IgA antibodies. Importantly, these findings indicate that epitope specificity of peanut-specific gut IgA does not distinguish between children with and without a peanut allergy.
Overall, the results of this study challenge previous assumptions that food-specific IgA is protective against food allergy.
- Liu, E. G., Zhang, B., Martin, V., et al. (2022). Food-specific immunoglobulin A does not correlate with natural tolerance to peanut or egg allergens. Science Translational Medicine. doi:10.1126/scitranslmed.abq0599.