Cytokine Signatures in Mucocutaneous and Ocular Behçet’s Disease

Giuseppe Lopalco,Luca Cantarini,Antonio Lopalco,Bruno Frediani,Giovanni Lapadula,Vincenzo Venerito,Claudia Fabiani,Mauro Galeazzi,Florenzo Iannone,Orso Maria Lucherini

doi:10.3389/fimmu.2017.00200

Abstract

Behçet’s disease (BD) is a multi-systemic inflammatory disorder consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis; however, many other organs may be affected. Several pro-inflammatory cytokines, mainly derived from Th1 and Th17 lymphocytes, seem to be involved in different pathogenic pathways leading to development of the clinical manifestations. On this basis, the primary aim of our study was to compare a core set of pro-inflammatory cytokines between patients with BD and healthy control (HC). The secondary goal was to evaluate potential correlations between these putative circulating biomarkers, the status of disease activity, and the specific organ involvement at the time of sample collection. Fifty-four serum samples were collected from 46 BD patients (17 males, 29 females, mean age 45.5 ± 11.3 years), and 19 HC (10 males, 9 females, mean age 43 ± 8.3 years). Twenty-five serum cytokines (APRIL/TNFS13, BAFF/TNFSF13B, sCD30/TNFRSF8, sCD163, Chitinase3-like1, gp130/sIL-6Rb, IFNb, sIL-6Ra, IL-10, IL-11, IL-19, IL-20, IL-26, IL-27 (p28), IL-28A/IFN-lambda2, IL-29/IFN-lambda1, IL-32, IL-34, IL-35, LIGHT/TNFSF-14, Pentraxin-3, sTNF-R1, sTNF-R2, TSLP, and TWEAK/TNFSF-12) were simultaneously quantified using a Bio-Rad cytokine bead arrays. Serum concentration of sTNF-R1 (p < 0.01) and sTNF-R2 (p < 0.01) resulted higher in both active and inactive BD than HC, while Chitinase3-like1 (p < 0.05) and gp130/sIL-6Rb (p < 0.01) serum levels were significantly higher in inactive BD, and IL-26 (p < 0.01) in active BD than HC. No differences were observed between inactive and active BD group. In addition, we observed that gp130/sIL-6Rb, sIL-6Ra, IL-35, and TSLP serum levels were significantly enhanced in patients with mucocutaneous manifestations plus ocular involvement (MO-BD) compared to subgroup with only mucocutaneous involvement (M-BD). Our findings may suggest a signature of IL-6, tumor necrosis factor-α as well as of Th17 response in BD patients due to increased levels of gp130/sIL-6Rb, sTNF-R1, sTNF-R2, IL-26, respectively. This evidence could contribute to improve the knowledge regarding the role of these citokines in the induction of specific BD clinical features.

Highlights

Behçet’s disease (BD) is a rare multisystemic inflammatory disorder clinically characterized by the “triple symptom complex,” consisting of recurrent oral aphthosis, genital ulcers, and relapsing bilateral uveitis
We found elevated levels of several inflammatory markers in BD patients including Chitinase3-like1, gp130/sIL-6Rb, IL-11, IL-26, sTNF-R1, and sTNF-R2 compared with healthy control (HC)
M-BD patients showed enhanced levels of Chitinase3-like1, sTNF-R1, and sTNF-R2 compared with HC as well as increased levels of gp130/ sIL-6Rb, sIL-6Ra, IL-11, IL-26, IL-35, sTNF-R1, sTNF-R2, and TSLP were found in MO-BD compared with HC

Summary

Introduction

Behçet’s disease (BD) is a rare multisystemic inflammatory disorder clinically characterized by the “triple symptom complex,” consisting of recurrent oral aphthosis, genital ulcers, and relapsing bilateral uveitis. Additional cytokines involved in mechanisms known to play a critical role in BD pathogenesis were recently associated to disease activity Molecules such as Chitinase3-like regulating monocytes differentiation, as well as antibacterial and type 17 responses, was observed to be upregulated in BD patients compared to healthy control (HC). This cytokine was seen to be associated to disease activity in BD, correlating positively with elevated IL-6 serum levels [17,18,19]

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