Cytokine and Chemokines Alterations in the Endemic Form of Pemphigus Foliaceus (Fogo Selvagem).

Rodolfo Pessato Timóteo,Jonatas Da Silva Catarino,Helioswilton Sales-Campos,Fernando Henrique Canhoto Alves,Carlo José Freire Oliveira,Ana Maria Roselino,Djalma Alexandre Alves Da Silva,Marcos Vinicius Silva,Virmondes Rodrigues Júnior

doi:10.3389/fimmu.2017.00978

Abstract

The endemic form (fogo selvagem-FS) of pemphigus foliaceus is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-1. Despite the array of findings, the role of chemokines and cytokines that dictate the immune response and disease outcome is still poorly investigated. Serum from 64 patients diagnosed with FS was used to draw and establish the levels of these molecules on this disease and establish the levels of these molecules with the severity of FS, and influence of treatment. In comparison to healthy subjects, FS patients, newly diagnosed and still without therapeutic intervention, had higher levels of IL-22 and CXCL-8, and reduced levels of IFN-γ, IL-2, IL-15, and CCL-11. Furthermore, treatment using immunosuppressant drugs augmented the production of IFN-γ, IL-2, CCL-5, and CCL-11 besides reducing the levels of IL-22 and CXCL-10. Immunosuppressive therapy seemed to have long-lasting effects on the production of higher amounts of IFN-γ, IL-2, and CCL-5, besides keeping lowered the levels of IL-22 in remission FS patients. Taken together, our findings suggest a putative role of IL-22 in the pathogenesis of FS. Finally, data presented here may contribute for better understanding the immune aspects that control disease outcome.

Highlights

Pemphigus is a severe and rare autoimmune disease characterized by antibodies targeting desmosomal proteins that are crucial to mucosal and epidermal integrity
Because of the importance of cytokines and chemokines on different physiological and pathological aspects, and due to the lack of a more consistent data concerning the production of these molecules in fogo selvagem” (FS) patients, the level of cytokines and chemokines was assessed in untreated FS patients and their healthy control counterparts
The following cytokines/chemokines were not detected: IL-13, TGF-β, IL-4, IL-9, and CCL3. These results suggest a complex interplay between cytokines and chemokines in the pathogenesis of FS

Summary

Introduction

Pemphigus is a severe and rare autoimmune disease characterized by antibodies targeting desmosomal proteins that are crucial to mucosal and epidermal integrity. Despite the role of antibodies targeting desmoglein, several other aspects are associated with the complex pathogenesis and susceptibility of pemphigus. Increased levels of T helper-2 (Th2) cytokines such as IL-4, IL-10, and IL-13 were already shown to be involved in the production of IgG4 by B-lymphocytes in both PF and PV patients. Those patients exhibited reduced levels of IL-2 and IFN-γ, resulting in suppressed expansion of Th1 lymphocytes, which suggests an inhibitory effect of Th2-cytokines, contributing to disease worsening [7]

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