Molecular characterization of an autoallergen, Hom s 1, identified by serum IgE from atopic dermatitis patients.
Atopy is a genetically determined disorder that affects 10%-20% of the population. Many symptoms of patients with atopy (allergic rhinitis, conjunctivitis, asthma, and anaphylaxis) result from events occurring after crosslinking of cell-bound IgE by per se innocuous environmental antigens. The frequently raised hypothesis that autosensitization can also be a pathogenetic factor in atopy, gained support by our recent demonstration of IgE antibodies against human proteins in atopic dermatitis patients. To unravel the molecular nature of IgE-defined autoantigens, we used serum IgE from atopic dermatitis patients to screen a human epithelial cDNA expression library. One of the cDNA-encoding IgE-reactive products contained 1501 bp of a 2274 bp open-reading frame finally identified by sequence analysis of two additional cDNA clones resulting from oligonucleotide screening. The IgE-defined autoantigen, designated Hom s 1, exhibited an almost complete sequence identity with a recently described antigen recognized by cytotoxic T cells of a squamous cell carcinoma patient. Purified recombinant Hom s 1 specifically bound IgE from patients with severe atopy. When used as immunogen in rabbits, recombinant Hom s 1 gave rise to an anti-serum that reacted with a cytoplasmic protein exhibiting a broad cellular and tissue reactivity (skin, lung >> gastrointestinal tract >> muscle, brain) and identified a 55 kDa protein in blotted serum IgE preparations. The attractive possibility remains that the Hom s 1-triggered IgE response contributes to the events resulting in allergic tissue inflammation. If so, the respective recombinant molecule may serve as a paradigmatic tool for the diagnosis and treatment of patients with "intrinsic" atopy.
Valenta
R
R
Institute of General and Experimental Pathology, Vienna General Hospital, University of Vienna Medical School, Austria.
Natter
S
S
Seiberler
S
S
Wichlas
S
S
Maurer
D
D
Hess
M
M
Pavelka
M
M
Grote
M
M
Ferreira
F
F
Szepfalusi
Z
Z
Valent
P
P
Stingl
G
G
D000485:Allergens / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D001324:Autoantigens / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification*; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology*; D033681:Mitochondrial Membrane Transport Proteins; D008969:Molecular Sequence Data; D013347:Subcellular Fractions / Q000737:chemistry / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; D000939:Epitopes; C116241:MICU1 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D007073:Immunoglobulin E