Abstract
Pemphigus is an autoimmune disease in which IgG auto-antibodies (auto-ab) against the desmosomal cadherins desmoglein (Dsg) 3 and Dsg1 cause loss of epidermal keratinocyte adhesion. Aim of this study was to investigate cytokines derived from antigen-presenting cells (APC) and their relation to CD4+ T cell subpopulations and to the auto-ab response in pemphigus. In this regard, patients with pemphigus were compared to patients with myasthenia gravis (MG), an unrelated auto-ab–mediated autoimmune disease, and healthy controls. In pemphigus and MG, the plasma concentrations of the APC-derived immunomodulatory cytokine IL-27 were highly increased. Strikingly, IL-27 strongly correlated with Dsg-specific IgG auto-ab titers. T helper (Th) 17 cells were augmented in both pemphigus and MG patients while T follicular helper (Tfh) cells, which are essential in providing B cell help, were increased only in pemphigus along with increasing plasma concentrations of IL-21, a cytokine produced by Th17 and Tfh cells. Moreover, we could detect Dsg3-specific autoreactive T cells producing IL-21 upon ex vivo stimulation with Dsg3. These findings suggest that IL-27 and IL-21-producing T cells, are involved in the pathogenesis of pemphigus. The further characterization of IL-21-producing T cells and of the role of IL-27 will lead to a more defined understanding of the auto-ab response in pemphigus.
Highlights
Pemphigus is an antibody-mediated autoimmune disease in which auto-ab mainly directed against the desmosomal cadherin Desmoglein (Dsg) 3 and Dsg1 cause loss of keratinocyte adhesion in the human skin
We investigated the plasma concentrations of the antigen-presenting cells (APC)-derived immunomodulatory cytokine IL-27 and the pro-inflammatory cytokines IL-6 and tumor necrosis factor (TNF)-α in active and remitting pemphigus patients, myasthenia gravis (MG) patients and healthy controls (HC)
We show that IL-27 plasma concentrations are increased in pemphigus and in MG, an unrelated auto-ab mediated neurological autoimmune disease (Fig 1A)
Summary
Pemphigus is an antibody (ab)-mediated autoimmune disease in which auto-ab mainly directed against the desmosomal cadherin Desmoglein (Dsg) 3 and Dsg cause loss of keratinocyte adhesion in the human skin. This process, called acantholysis, presents clinically with flaccid blisters and erosions of the skin and mucous membranes [1, 2]. Since the precise immunological events resulting in the breakdown of self-tolerance in pemphigus are not yet completely understood, therapeutic options are mainly confined to broad systemic immunosuppression often causing significant side effects and comorbidities [3]. T Follicular Helper Cells and Interleukin-27 in Pemphigus PLOS ONE | DOI:10.1371/journal.pone.0148919 February 12, 2016
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