title: Is Grover's disease an autoimmune dermatosis?
abstract: Grover's disease (GD) is a transient or persistent, monomorphous, papulovesicular, asymptomatic or pruritic eruption classified as non-familial acantholytic disorder. Contribution of autoimmune mechanisms to GD pathogenesis remains controversial. The purpose of this study was to investigate antibody-mediated autoimmunity in 11 patients with GD, 4 of which were positive for IgA and/or IgG antikeratinocyte antibodies by indirect immunofluorescence. We used the most sensitive proteomic technique for an unbiased analysis of IgA- and IgG-autoantibody reactivities. Multiplex analysis of autoantibody responses revealed autoreactivity of all 11 GD patients with cellular proteins involved in the signal transduction events regulating cell development, activation, growth, death, adhesion and motility. Semiquantitative fluorescence analysis of cultured keratinocytes pretreated with sera from each patient demonstrated decreased intensity of staining for desmoglein 1 and/or 3 and PCNA, whereas 4 of 10 GD sera induced BAD expression, indicating that binding of autoantibodies to keratinocytes alters expression/function of their adhesion molecules and activates apoptosis. We also tested the ability of GD sera to induce visible alterations of keratinocyte shape and motility in vitro but found no specific changes. Thus, our results demonstrated that humoral autoimmunity in GD can be mediated by both IgA and IgG autoantibodies. At this point, however, it is impossible to conclude whether these autoantibodies cause or are caused by the disease. Antidesmoglein antibodies may be triggered by exposure to immune system of sequestered antigens due to disintegration of desmosomes during primary acantholysis. Clarifying aetiology of GD will help improve treatment, which currently is symptomatic and of marginal effectiveness.
authors.affiliation: Department of Dermatology, University of California, Irvine, CA, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Phillips
authors.forename: Mina
authors.initials: M
authors.lastname: Kalantari-Dehaghi
authors.forename: Steve
authors.initials: S
authors.lastname: Marchenko
authors.forename: Alex I
authors.initials: AI
authors.lastname: Chernyavsky
authors.forename: Valentin
authors.initials: V
authors.lastname: Galitovskiy
authors.forename: Vivian
authors.initials: V
authors.lastname: Gindi
authors.forename: Sookhee
authors.initials: S
authors.lastname: Chun
authors.forename: David
authors.initials: D
authors.lastname: Paslin
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Grando
mesh_terms: D000051:Acantholysis / Q000175:diagnosis / Q000276:immunology*; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D003896:Desmosomes / Q000378:metabolism; D006801:Humans; D007057:Ichthyosis / Q000175:diagnosis / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D008875:Middle Aged; D012871:Skin Diseases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007074:Immunoglobulin G
keywords: Grover's disease; autoantibody; keratinocytes; proteomics