Expression of Periostin (raw data).

Background
Scabies is a debilitating parasitic skin disease caused by the obligate parasitic mite Sarcoptes scabiei, which inhabits the upper layers of the epidermis. In over 90% of affected individuals intense itching is the primary clinical symptom. This is accompanied by other delayed-type hypersensitivity responses. Persistent scratching due to the itch compromises skin integrity, facilitating the entry of pathogenic bacteria. Combined with immune-modulatory factors secreted by the mites, this creates a permissive environment for bacterial colonisation often leading to secondary complications. Effective treatment of scabies-associated itch could significantly reduce these complications and improve patients’ quality of life. However, current antipruritic therapies are inadequate: in most cases, antihistamines provide little relief for scabies-related itch, and systemic corticosteroids are generally contraindicated. Thus, there is a critical need for targeted therapies, yet progress has been hindered by a limited understanding of the underlying pathobiology of scabies-induced pruritus.
Methodology/Principal Findings
We investigated the expression of itch-associated mediators - encompassing both histaminergic and non-histaminergic pathways - using immunohistochemistry in a porcine scabies model. Skin biopsies were collected at multiple time points during the course of infection. We observed upregulated expression of key non-histaminergic itch receptors PAR-2 and MRGPRX2, as well as the mediator tryptase, following infection. Additionally, levels of the pruritogenic cytokine IL-31 and periostin, a molecule that may promote IL-4, IL-13 and IL-31 expression were elevated, as were substance P and its receptor NK-1R. In addition, the expression of histamine, the primary mediator of the histaminergic itch pathway, was also increased. Notably, reduced expression of β tubulin III across all time points suggests direct mite-induced neuroinflammation. Our findings may serve as a valuable basis for future drug development efforts focused on specific treatment of scabies-associated itch.
Conclusions/Significance
Our data suggest that both the histaminergic and non-histaminergic pathways may be involved in scabies itch. Further research is needed to better understand the complex interplay between these pathways and to identify therapeutic targets for scabies-related itch.

背景
疥疮（scabies）是由寄生于表皮上层的专性寄生疥螨（Sarcoptes scabiei）所致的致残性寄生虫皮肤病。超过90%的受累个体以剧烈瘙痒为主要临床症状，同时伴随其他迟发型超敏反应（delayed-type hypersensitivity responses）。因瘙痒引发的持续搔抓会破坏皮肤完整性，便于病原菌（pathogenic bacteria）侵入；结合疥螨分泌的免疫调节因子（immune-modulatory factors），这会为细菌定植（bacterial colonisation）构建适宜环境，常导致继发并发症（secondary complications）。有效治疗疥疮相关性瘙痒，可显著降低此类并发症并改善患者生活质量。然而当前止痒疗法（antipruritic therapies）存在不足：多数情况下抗组胺药（antihistamines）对疥疮相关瘙痒的缓解效果甚微，全身性糖皮质激素（systemic corticosteroids）通常为禁忌证。因此，临床上亟需靶向治疗方案（targeted therapies），但由于对疥疮诱导瘙痒的潜在病理生物学（pathobiology）机制认知有限，相关研究进展受到阻碍。
方法学/主要研究结果
本研究在猪疥疮模型（porcine scabies model）中，采用免疫组化（immunohistochemistry）技术，探究了涵盖组胺能与非组胺能通路的瘙痒相关介质的表达情况。在感染进程的多个时间点采集皮肤活检样本（skin biopsies）。研究观察到，感染后关键非组胺能瘙痒受体蛋白酶激活受体2（PAR-2）、MAS相关G蛋白偶联受体X2（MRGPRX2），以及介质类胰蛋白酶（tryptase）的表达均出现上调。此外，致痒细胞因子白细胞介素31（IL-31）、可促进IL-4、IL-13及IL-31表达的骨膜蛋白（periostin）的水平均升高，P物质（substance P）及其受体神经激肽1受体（NK-1R）的表达也同样上调。同时，组胺能瘙痒通路的主要介质组胺（histamine）的表达也有所增加。值得注意的是，各时间点下β微管蛋白III（β tubulin III）的表达均降低，提示疥螨可直接诱导神经炎症（neuroinflammation）。本研究结果可为未来针对疥疮相关性瘙痒的特异性治疗药物开发提供重要参考依据。
结论与意义
本研究数据表明，组胺能与非组胺能通路均可能参与疥疮瘙痒的发生过程。未来仍需开展进一步研究，以更好地阐明这些通路之间的复杂相互作用，并明确疥疮相关瘙痒的治疗靶点。