Review article
Autoantibodies in atopic dermatitis

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Abstract

Recent progress in the autoimmune aspects of atopic dermatitis has clarified that patients with atopic dermatitis develop IgE-class autoantibodies mainly against intracellular proteins. The cloning of cDNAs encoding autoallergens with human expression cDNA libraries and serum IgE from atopic dermatitis patients has unraveled the molecular characteristics of IgE-binding autoantigens. Some patients with atopic dermatitis also have IgG-class autoantibodies, especially anti-nuclear antibodies. One of the nuclear autoantigens was identified as DFS70/transcription coactivator p75. In addition, p80-coilin in nuclear coiled bodies is also targetted. Several lines of evidence suggest that a subset of atopic dermatitis may be associated with an autoimmune response.

Introduction

Atopy is an immune disorder of hypersensitivity to common, rather innocuous environmental antigens derived from agents such as pollen and house dust mites. It is the leading cause of asthma, rhinitis, and atopic dermatitis (AD). However, allergic mechanisms do not play a central pathogenic role in AD [1], [2]. For example, elevated total serum IgE or antigen-specific sensitivities are not essential for the development of dermatitis and are frequently absent in those without coexisting respiratory atopy. Hanifin summarized four current hypotheses concerning the cause of AD in his review [3]: (1) cyclic nucleotide dysfunction; (2) the role of superantigen; (3) IgE-mediated allergy to airborne and food allergens; and (4) autoimmunity to self-antigens.

During the past 10 years, several IgE-binding autoantigens have been characterized using biochemical and molecular biological methods and there is increasing evidence that IgE-mediated reactivity against autoantigens could play a role in the pathology of severe atopic conditions [4], [5]. Recent progress in the autoimmune and autoallergic aspects of AD are reviewed in this article.

Section snippets

Anti-IgE autoantibodies

Circulating anti-IgE autoantibodies have been demonstrated in the sera of a large portion of individuals with atopic disease [6], [7], [8] and to a lesser extent in normal individuals [9], [10]. According to previous reports, the proportion of the anti-IgE autoantibodies in AD patients was >50% [8] or >80% [7], [11]. However, one of the major problems in determining anti-IgE antibodies is the fact that the antigen (IgE) coexists with the autoantibody in approximately equimolar concentrations,

IgE-class autoantigens

More than 50 years ago, it was reported that human dander extract can elicit immediate-type skin reactions in AD patients and that human skin extracts can induce the proliferation of leukocytes in AD patients [5]. After 1990, cloning and sequencing of environmental allergen-encoding cDNAs revealed that some environmental allergens shared structural and functional similarities with human proteins. Many investigators have been using an isolating system of cDNA encoding an allergenic protein with

Antinuclear antibodies

In systemic rheumatic diseases such as systemic lupus erythematosus, Sjogren syndrome, and scleroderma, the profile of serum antinuclear antibodies (ANA) in the patients is well known to be highly characteristic for each disease [31]. Recently, several laboratories in Japan have reported the presence of ANA in some patients with AD [32], [33], [34], [35]. According to their reports, the characteristics of ANA in patients with AD can be summarized as follows: (1) The positivity is 25–35%. (2)

Anti-DFS70 antibodies and DFS70 antigen

DFS70 is a major IgG-class autoantibody/autoantigen system in AD that we recently reported [36]. In immunohistochemistry, sera from AD patients displayed a characteristic pattern showing a nuclear distribution of dense, fine speckles as the most common ANA pattern (Fig. 1). The sera also recognized a 70-kDa protein on immunoblots (Fig. 2), and therefore the antigen was termed dense fine speckles 70 (DFS70).

Initially, the cDNA encoding DFS70 was cloned with ANA from an interstitial cystitis (IC)

Anti-p80-coilin antibodies

In this review, I would like to describe another autoantibody specificity, p80-coilin, that was characterized recently in our laboratory [44]. Although the autoantibodies are also recognized in other diseases [45], [46], our current data suggest that a number of AD patients have the antibodies. p80-coilin is the major autoantigen in the nuclear coiled body which is a round structure found in most eukaryotic cells [47]. Autoantibodies to p80-coilin recognize mostly one or two nuclear bodies with

Pathological significance of autoantibodies in AD

Recent studies on autoimmunity in AD suggest that a subset of AD may be associated with an autoimmune response. Valenta et al. noted in their review [5] two possible pathomechanisms of auto allergy. One is that autoallergens may cross-link effector cell-bound IgE autoantibodies and lead to immediate-type symptoms by the release of inflammatory mediators. Second is that IgE-mediated presentation of autoallergens may activate autoreactive T cells to release proinflammatory cytokines, inducing

Acknowledgements

This work was partly supported by a grant (11670823) from the Ministry of Education, Science, and Culture of Japan and by a grant from Kato Memorial Bioscience Foundation.

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