The IgE-reactive autoantigen Hom s 2 induces damage of respiratory epithelial cells and keratinocytes via induction of IFN-gamma.
Hom s 2, the alpha-chain of the nascent polypeptide-associated complex, is an intracellular autoantigen that has been identified with IgE autoantibodies from atopic dermatitis patients. We investigated the humoral and cellular immune response to purified recombinant Hom s 2 (rHom s 2). rHom s 2 exhibited IgE reactivity comparable to exogenous allergens, but did not induce relevant basophil cell degranulation. The latter may be attributed to the fact that patients recognized single epitopes on Hom s 2 as revealed by IgE epitope mapping with rHom s 2 fragments. In contrast to exogenous allergens, rHom s 2 had the intrinsic ability to induce the release of IFN-gamma in cultured peripheral blood mononuclear cells from atopic as well as non-atopic individuals. IFN-gamma-containing culture supernatants from Hom s 2-stimulated peripheral blood mononuclear cells caused disintegration of respiratory epithelial cell layers and apoptosis of skin keratinocytes, which could be inhibited with a neutralizing anti-IFN-gamma antibody. Our data demonstrate that the Hom s 2 autoantigen can cause IFN-gamma-mediated cell damage.
Mittermann
Irene
I
Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Reininger
Renate
R
Zimmermann
Maya
M
Gangl
Katharina
K
Reisinger
Jürgen
J
Aichberger
Karl J
KJ
Greisenegger
Elli K
EK
Niederberger
Verena
V
Seipelt
Joachim
J
Bohle
Barbara
B
Kopp
Tamara
T
Akdis
Cezmi A
CA
Spitzauer
Susanne
S
Valent
Peter
P
Valenta
Rudolf
R
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000737:chemistry*; D001324:Autoantigens / Q000737:chemistry*; D004847:Epithelial Cells / Q000166:cytology; D018604:Epitope Mapping; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry*; D007371:Interferon-gamma / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged
D000485:Allergens; D001324:Autoantigens; C529681:Hom s 2 autoantigen, human; D007073:Immunoglobulin E; D007371:Interferon-gamma