A Role for Glycans in Bla g 2 Cockroach Allergen-Induced Allergic Responses

Rationale: Exposure to German cockroaches is associated with IgE sensitization to cockroach allergen and increased risk for allergic asthma. Recombinant peptide-based cockroach allergens have been produced that are associated with allergic responses, however, little is known about other cockroach allergen factors that contribute to allergic responses. We sought to identify additional/novel components in cockroach extract (CRE) that contribute to the induction of cockroach sensitization and asthma.

Methods: Profiling of N-linked glycans on purified Bla g 2 was performed by MALDI-TOF mass spectrometry. The binding capacity of serum IgE antibodies to glycan from individuals with positive reactivity to Bla g 2 (n=22) was detected by ELISA. Glycan-induced histamine release in human basophils was examined.

Results: N-linked hybrid- and complex-typed di-fucose modified glycans with mannose-, galactose-, and/or N-acetyl glucosamine-terminated moiety on Bla g 2 was identified by mass spectrometry. Of five selected individuals with strong reactivity to Bla g 2, four showed a significant reduction in IgE binding to deglycosylated Bla g 2 compared to native Bla g 2. Furthermore, Bla g 2 deglycosylation reduced histamine release in passively sensitized human basophils as compared to Bla g 2 (6.0±0.5% vs 12.0±1.1%, p<0.019). Interestingly, our initial study suggests that glycan alone appears to prevent spontaneous histamine release in basophils.

Conclusions: Our studies heighten the potential involvement of glycans in cockroach allergen-induced sensitization and asthma. However, further studies are clearly needed to expand upon this observation.