Morais K L, Miyamoto D, Orfali R L, Maruta C W, Santi C G, Sotto M N, da Silva L F F, Branco A C C C, Sato M N, Aoki V
Department of Dermatology, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP, Brazil.
Laboratory of Medical Investigation-56, Department of Dermatology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
J Eur Acad Dermatol Venereol. 2020 Dec;34(12):2890-2897. doi: 10.1111/jdv.16730. Epub 2020 Jul 7.
Pemphigus herpetiformis (PH) is a rare clinical subtype of pemphigus with the presence of urticarial plaques, severe pruritus, rare acantholysis and eosinophilic spongiosis.
The aim of this study was to investigate the influence of IL-31 and pro-inflammatory cytokines/chemokines in the pathogenesis of PH.
Twenty-five patients with PH and three groups: pemphigus foliaceus (PF = 14), pemphigus vulgaris (PV = 15) and healthy controls (HC = 20) were selected for this study. The groups were analysed by immunohistochemistry utilizing IL-31, IL-31RA, IL-4, IL-17 and TNF-α antibodies. Serum levels of IL-4, IL-13, TNF, CXCL8, CCL5 and CCL2 were evaluated by cytometric bead array.
Analysis of IL-31 family of PH patients revealed the following findings: (i) Enhanced in situ expression of IL-31 in PH samples, compared to PF and to PV (epidermis); (ii) Cutaneous IL-31RA expression in PH samples was higher than in PF, PV and HC groups (epidermis and dermis); (iii) PF patients that evolved to PH showed significant increased IL-31RA epidermal expression during the PH phase. Profile of pro-inflammatory cytokines (IL-4, IL-17 and TNF-α) in PH patients' skin exhibited: (i) Enhanced IL-4 expression, when compared to patients with PF (epidermis and dermis) and with PV (epidermis); (ii) Augmented IL-17 expression than PF and PV patients (epidermis); (iii) Augmented expression of TNF-α when compared to PF at the epidermal level. Evaluation of circulating cytokines and chemokines showed higher levels of CXCL8 and CCL2 in PH sera compared to HC group.
IL-31 and IL-31RA, cytokines related to pruritus, and pro-inflammatory chemokines (CXCL8 and CCL2) seem to exert a role in the pathogenesis of PH. These findings support future studies to clarify the role of IL-31 pathway as a potential therapeutic target for patients with PH.
疱疹样天疱疮（PH）是天疱疮的一种罕见临床亚型，表现为荨麻疹样斑块、严重瘙痒、罕见棘层松解和嗜酸性海绵形成。
本研究旨在探讨白细胞介素-31（IL-31）和促炎细胞因子/趋化因子在PH发病机制中的作用。
本研究选取了25例PH患者以及三组对照：落叶型天疱疮（PF，14例）、寻常型天疱疮（PV，15例）和健康对照（HC，20例）。采用免疫组织化学方法，利用IL-31、IL-31受体A（IL-31RA）、IL-4、IL-17和肿瘤坏死因子-α（TNF-α）抗体对各组进行分析。通过细胞计数珠阵列评估血清中IL-4、IL-13、TNF、CXC趋化因子配体8（CXCL8）、CC趋化因子配体5（CCL5）和CC趋化因子配体2（CCL2）的水平。
对PH患者的IL-31家族分析发现以下结果：（i）与PF和PV（表皮）相比，PH样本中IL-31的原位表达增强；（ii）PH样本中皮肤IL-31RA的表达高于PF、PV和HC组（表皮和真皮）；（iii）演变为PH的PF患者在PH阶段表皮IL-31RA表达显著增加。PH患者皮肤中促炎细胞因子（IL-4、IL-17和TNF-α）谱显示：（i）与PF患者（表皮和真皮）和PV患者（表皮）相比，IL-4表达增强；（ii）比PF和PV患者（表皮）IL-17表达增加；（iii）与PF相比，表皮水平TNF-α表达增加。循环细胞因子和趋化因子评估显示，与HC组相比，PH血清中CXCL8和CCL2水平更高。
与瘙痒相关的细胞因子IL-31和IL-31RA以及促炎趋化因子（CXCL8和CCL2）似乎在PH的发病机制中发挥作用。这些发现支持未来开展研究以阐明IL-31通路作为PH患者潜在治疗靶点的作用。
