In chronic idiopathic urticaria autoantibodies against Fc epsilonRII/CD23 induce histamine release via eosinophil activation.
BACKGROUND
Chronic idiopathic urticaria is a common skin disorder characterized by recurrent, transitory, itchy weals for more than 6 weeks. An autoimmune origin has been suggested based on the findings of auto-antibodies (Abs) directed against either the alpha subunit of the high-affinity IgE receptor or the IgE molecule in nearly half of the patients.


OBJECTIVE
To identify other autoantigen targets in patients with chronic idiopathic urticaria.


METHODS
We used pooled IgG derived from 133 patients with chronic idiopathic urticaria to screen a random peptide library to identify disease-relevant autoantigen peptides. Among the identified peptides, one was recognized by the vast majority of patients' sera. Abs against this peptide were affinity purified from the patients' sera and assayed for their ability to induce histamine release from basophils.


RESULTS
We identified a peptide that showed similarity with the low-affinity IgE receptor (Fc epsilonRII/CD23) expressed on lymphomonocytes and eosinophils. Anti-peptide IgG Abs purified from the patients' sera bound cell surface CD23 and were able to induce histamine release from basophils. This effect appeared to be mediated by the release of major basic protein from eosinophils upon engagement of CD23. The same effects were obtained with the sera from mice immunized with the CD23 peptide.


CONCLUSIONS
Our results indicate that patients with chronic idiopathic urticaria have Abs against CD23 and that eosinophils, which infiltrate the skin of these patients, play a crucial role in maintaining the disease through the release of major basic protein upon engagement of the low-affinity IgE receptor by such auto-Abs.
Puccetti
A
A
Department of Experimental Medicine, University of Genova, Genova, Italy.
Bason
C
C
Simeoni
S
S
Millo
E
E
Tinazzi
E
E
Beri
R
R
Peterlana
D
D
Zanoni
G
G
Senna
G
G
Corrocher
R
R
Lunardi
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis; D016009:Chi-Square Distribution; D002908:Chronic Disease; D047093:Eosinophil Major Basic Protein / Q000032:analysis; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006636:Histamine Release; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D017455:Receptors, IgE / Q000032:analysis / Q000276:immunology*; D018709:Statistics, Nonparametric; D014581:Urticaria / Q000276:immunology*
D001323:Autoantibodies; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017455:Receptors, IgE; D047093:Eosinophil Major Basic Protein