- This study examined whether glycosylation patterns specific to allergic disease exist for IgE and, if so, whether those patterns influence the biologic activity of IgE
- Specific glycosylation patterns did distinguish allergic from non-atopic IgE, and the galactose and sialic acid contents of IgE were strong predictors of allergic disease
- In animal models of systemic anaphylaxis and food allergy, removal of sialic acid from IgE weakened allergic reactions and adding sialic acid exacerbated them
- A fusion protein that targets sialic acid on IgE-bearing cells dampened allergic inflammation, and results were similar in a mouse model
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Immunoglobulin E (IgE) is essential to the allergic cascade, but allergen-specific IgE is also detected in many people who don't experience allergic symptoms. It's unclear why IgE causes allergic disease in only some circumstances.
Principal Investigator Robert M. Anthony, PhD, Research Fellow Kai-Ting C. Shade, PhD, and Attending Physician Michelle Conroy, MD, of the Center for Immunology and Inflammatory Diseases within the Division of Rheumatology, Allergy and Immunology at Massachusetts General Hospital, and colleagues noted that the biologic activity of IgG is affected by the composition of the glycans attached to it. The composition influences the outcome of rheumatoid arthritis and many other diseases, and the team investigated whether the same might be true for IgE.
In Nature, the researchers report that they did indeed identify allergy-specific glycosylation patterns for IgE. What's more, their findings led them to a novel strategy for the diagnosis and treatment of allergic diseases.
Glycans on IgE
It's known that there are seven glycosylation sites on human IgE. One is unoccupied, one is occupied by oligomannose and the other five are occupied by a complex of N-acetyl glucosamine, mannose, fucose, galactose and sialic acid.
The researchers compared IgE from individuals with peanut allergy with IgE from non-atopic individuals. They found:
- Fucose content was similar between the two groups
- Levels of galactose and N-acetyl glucosamine were substantially increased on non-atopic IgE
- Sialic acid was increased on allergic IgE
- The galactose and sialic acid contents of IgE were strong predictors of allergic disease
In mouse models of systemic anaphylaxis and food allergy, removal of sialic acid from IgE dampened allergic reactions and adding sialic acid exacerbated them. Further experiments confirmed that removing sialic acid from IgE attenuates its effector functions.
A Potential New Therapeutic Strategy
By attaching a neuraminidase enzyme to the IgE receptor, the researchers created a fusion protein that directs sialic acid removal specifically to IgE-bearing cells. Treatment with the fusion protein markedly reduced allergic reactions in the mouse model of systemic anaphylaxis.
Further research that quantifies sialic acid on IgE may also lead to a more accurate diagnosis of allergic diseases.
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