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.
Aichberger
Karl J
KJ
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.
Mittermann
Irene
I
Reininger
Renate
R
Seiberler
Susanne
S
Swoboda
Ines
I
Spitzauer
Susanne
S
Kopp
Tamara
T
Stingl
Georg
G
Sperr
Wolfgang R
WR
Valent
Peter
P
Repa
Andreas
A
Bohle
Barbara
B
Kraft
Dietrich
D
Valenta
Rudolf
R
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