Staphylococcal exotoxins and nasal polyposis: analysis of systemic and local responses.
BACKGROUND
Staphylococcal exotoxins have been implicated in the pathogenesis of several chronic inflammatory diseases including atopic dermatitis (AD), asthma, and, most recently, chronic rhinosinusitis with nasal polyposis (CRS/NP). In severe AD, these toxins act both as superantigens (SAg), triggering massive T-cell activation, and as conventional allergens, triggering toxin-specific immunoglobulin E (IgE) in the serum. In CRS/NP, evidence for both processes has been reported but it is unclear whether these processes are linked. The aim of this study was to correlate SAg activity as inferred by staphylococcal-specific T-cell receptor (TCR) V-beta expansion in the polyp and blood of CRS/NP patients with staphylococcal-specific anti-IgE antibodies in the serum.


METHODS
IgE antibodies to staphylococcal exotoxin A (SEA), staphylococcal exotoxin B (SEB), and toxic shock syndrome toxin (TSST) 1 were measured in the serum of 12 individuals with CRS/NP before functional endoscopic sinus surgery. Flow cytometry was used to analyze the SEA, SEB, and TSST-1-specific TCR V-beta domains on the T cells from the polyp and blood of these patients.


RESULTS
Serum SEA-, SEB-, and TSST-1-specific IgE antibodies were detected in 0/12 (0%), 6/12 (50.0%), and 9/12 (75%) of CRS/NP patients, respectively. Evidence of SAg effect in the polyp lymphocytes (TCR V-beta expansion in both CD4+ and CD8+ subsets) was noted in 7/12 (58.3%) patients. Five of 6 CRS/NP patients had overlapping evidence of a systemic IgE response and TCR V-beta expansion, suggestive of exposure to the same exotoxin. No patients had evidence a SAg effect in blood lymphocytes. Nine of 12 subjects also had coexistent asthma.


CONCLUSIONS
These results provide evidence for a local SAg effect in 7/12 (58.3%) polyp patients and establish a positive correlation of V-beta expansion with the presence of corresponding toxin-specific IgE in the serum.
Tripathi
Anju
A
Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Kern
Robert
R
Conley
David B
DB
Seiberling
Kristin
K
Klemens
Julie C
JC
Harris
Kathleen E
KE
Suh
Lydia
L
Huang
Jie
J
Grammer
Leslie C
LC
D000328:Adult; D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D005098:Exotoxins; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012220:Rhinitis / Q000382:microbiology; D012852:Sinusitis / Q000382:microbiology; D013210:Staphylococcus / Q000276:immunology* / Q000472:pathogenicity*; D018089:Superantigens
D005098:Exotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D007073:Immunoglobulin E