Hom s 4, an IgE-reactive autoantigen belonging to a new subfamily of calcium-binding proteins, can induce Th cell type 1-mediated autoreactivity.
Skin inflammation in atopic dermatitis starts with Th2 and IgE-mediated responses against exogenous allergens and, for unknown reasons, resembles features of a Th1-driven reaction in the chronic stages. We report the characterization of a human protein, Hom s 4, recognized by IgE autoantibodies from atopic dermatitis patients. The complete Hom s 4 cDNA codes for a 54-kDa basic protein containing two typical calcium-binding domains separated by an unusually long alpha-helical domain. Therefore, Hom s 4 and homologous proteins found by sequence comparison in mice, fruit flies, and nematodes constitute a novel subfamily of calcium-binding proteins. Using Hom s 4-specific Abs, it is demonstrated that the protein is strongly expressed within epidermal keratinocytes and dermal endothelial cells. Purified Hom s 4 showed IgE cross-reactivity with exogenous calcium-binding allergens from plants and fish but, in contrast to the exogenous allergens, induced only weak histamine release from patient basophils. However, the analysis of Hom s 4-specific cytokine and humoral immune responses indicated that Hom s 4 strongly induces Th1 responses which are accompanied by the release of IFN-gamma, a cytokine implicated in epithelial cell damage. Hom s 4-induced IFN-gamma production was found in normal individuals, in patients with chronic inflammatory skin diseases and in Th2-prone atopic persons, suggesting that Hom s 4 represents a protein with an intrinsic property to induce Th1-mediated autoreactivity. It may thus contribute to chronic skin inflammation in atopic as well as in nonatopic persons.
Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Vienna General Hospital, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Karl J
KJ
Aichberger
Irene
I
Mittermann
Renate
R
Reininger
Susanne
S
Seiberler
Ines
I
Swoboda
Susanne
S
Spitzauer
Tamara
T
Kopp
Georg
G
Stingl
Wolfgang R
WR
Sperr
Peter
P
Valent
Andreas
A
Repa
Barbara
B
Bohle
Dietrich
D
Kraft
Rudolf
R
Valenta
D000328:Adult; D000368:Aged; D000485:Allergens / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D052179:Antigens, Plant; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D027682:Cation Transport Proteins; D002460:Cell Line; D003429:Cross Reactions; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000276:immunology / Q000378:metabolism; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000276:immunology / Q000378:metabolism; D013347:Subcellular Fractions / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*
D000485:Allergens; D052179:Antigens, Plant; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D027682:Cation Transport Proteins; C116241:MICU1 protein, human; D033681:Mitochondrial Membrane Transport Proteins; C468525:Phl p 7 allergen; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D007371:Interferon-gamma