October 9, 2016

Antibodies and Superantibodies in Chronic Rhinosinusitis with Nasal Polyps

Article in Press
Abstract
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease (AERD) is a severe form of CRSwNP in which nearly all patients express anti-SAEs.

Objectives
We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions (FRs).
Methods
Labeled Staphylococcal enterotoxin A (SEA), SED and SEE were used to isolate single SAE-specific B cells from the nasal polyps of three AERD patients by FACS. Recombinant antibodies with “matched” heavy- and light-chains were cloned as IgG1, and those of high-affinity for specific SAEs, assayed by ELISA and surface plasmon resonance (SPR), were re-cloned as IgE and Fab. The activities of the IgEs were tested in basophil degranulation assays.
Results
Thirty-seven SAE-specific, IgG or IgA-expressing B cells were isolated and yielded six anti-SAE clones, two each for SEA, SED and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize non-overlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation and IgG1 or Fab of each anti-SEE enhanced degranulation by the other anti-SEE.
Conclusions
SEE may activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to FRs of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1s may enhance the activity of anti-SEE IgEs as conventional antibodies via CDRs or simultaneously as conventional antibodies and as “superantibodies” via CDRs and FRs to SEEs in SEE-anti-SEE IgE-FcεRI complexes (Figure 7).
Article Tools

No comments:

Post a Comment