title: Nonsecretory IgA1 autoantibodies targeting desmosomal component desmoglein 3 in intraepidermal neutrophilic IgA dermatosis.
abstract: Intraepidermal neutrophilic IgA dermatosis, a rare skin disease entity manifested with blisters and pustules clinically and lower epidermal blister, acantholysis, and neutrophilic infiltration pathologically, was first reported in 1985. Although the disease is characterized by IgA autoantibodies targeting the epithelial cell surface component, the target antigen has not been determined. We investigated a patient with this disease by histopathology, direct and indirect immunofluorescence, immunoblotting, and immunoadsorption studies. The pustular lesion was characterized by blister at the lower epidermis, acantholysis, and neutrophilic infiltration. Nonsecretory IgA1 subclass autoantibodies targeting the lower epithelial cell surfaces were detected in the patient's skin and serum. The patient's IgA autoantibodies labeled a recombinant desmosomal protein desmoglein 3 on immunoblotting and the immunolabeling of epithelial cell surfaces was eliminated by preadsorption with desmoglein 3. Thus, desmoglein 3 is identified as a target antigen in intraepidermal neutrophilic IgA dermatosis. The ability of IgA1 autoantibodies to bind neutrophils may be responsible for the prominent neutrophilic infiltration observed histopathologically and for the pustular lesions observed clinically.
authors.affiliation: Department of Dermatology, Northwestern Univesity Medical School, Chicago, Illinois, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Kwon
authors.forename: X
authors.initials: X
authors.lastname: Ding
authors.forename: J A
authors.initials: JA
authors.lastname: Fairley
authors.forename: D T
authors.initials: DT
authors.lastname: Woodley
authors.forename: L S
authors.initials: LS
authors.lastname: Chan
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D015820:Cadherins / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D051184:Desmoglein 3; D000939:Epitopes; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007163:Immunosorbent Techniques; D008297:Male; D010392:Pemphigus / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D012867:Skin / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D000939:Epitopes; D007070:Immunoglobulin A; D011994:Recombinant Proteins