Ergun Ecem Zeliha, Aoki Rui, Horváth Orsolya N, Hartmann Daniela, Satoh Takashi K, Calabrese Laura, Aksu Ayşe Esra Koku, Gürel Mehmet Salih, Manav Vildan, Flaig Michael J, Sárdy Miklós, Ruzicka Thomas, French Lars E, Bağcı Işın Sinem
Department of Dermatology and Allergy, University Hospital of Munich, Ludwig-Maximilian-University (LMU), Munich, Germany.
Department of Dermatology, Haydarpaşa Training and Research Hospital, Health Science University, Istanbul, Turkey.
Exp Dermatol. 2023 Sep;32(9):1412-1419. doi: 10.1111/exd.14842. Epub 2023 Jun 1.
Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL-31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL-31 and its receptor IL-31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL-31 and IL-31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL-31RA-expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL-31/IL-31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL-31/IL-31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL-31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL-31/IL-31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL-31/IL-31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL-31/IL-31RA pathway in BP patients.
大疱性类天疱疮（BP）和寻常型天疱疮（PV）是两种主要的自身免疫性水疱性皮肤病。与PV不同，BP伴有剧烈瘙痒，提示致痒细胞因子IL-31可能参与其中。然而，BP和PV在瘙痒方面临床差异的潜在机制尚未完全明确。为了比较BP和PV患者皮损皮肤（包括周围神经）中IL-31及其受体IL-31RA的表达水平，对BP和PV患者以及健康对照（HC）的皮肤样本进行了IL-31和IL-31RA的免疫组织化学染色。使用ImageJ分析表皮和周围神经中IL-31RA的表达面积，并手动定量真皮浸润细胞中IL-31/IL-31RA阳性细胞的百分比。定量分析显示，与PV和HC相比，BP患者表皮和真皮浸润中的IL-31/IL-31RA表达显著增加。当比较晚期水疱性皮损时，BP和PV之间的差异更加明显。与PV皮损相比，BP皮损中的周围神经呈现出显著更高的IL-31RA表达。总之，我们发现与PV相比，BP皮损（包括周围神经）中IL-31/IL-31RA的表达显著增加。这些结果提示IL-31/IL-31RA信号通路可能在BP和PV在瘙痒促进和局部皮肤炎症方面的差异中发挥作用，增加了针对BP患者的IL-31/IL-31RA途径进行治疗的可能性。
