BackgroundAlopecia areata (AA) is a chronic, nonscarring hair‐loss disorder associated with significant quality‐of‐life impairment and limited treatment options. AA has been recently linked to atopy and shown to exhibit both Th1‐ and Th2‐driven inflammation. However, a comprehensive molecular and cellular characterization across blood and scalp compartments in both atopic and nonatopic patients is lacking.MethodsLesional and nonlesional scalp biopsies obtained from AA patients with (n = 16) or without (n = 20) atopic history, and 17 demographically matched healthy controls were analyzed with RNA‐seq, RT‐PCR, and immunohistochemistry. Flow cytometry was also performed on peripheral blood mononuclear cells (PBMCs) from a subset of patients. Differential expression was defined using |fold‐change| > 1.5 and false‐discovery rate <0.05.ResultsAA scalp exhibited robust upregulation of Th1‐ (IFNG, CXCL9, CXCL10, CXCL11) and Th2‐related products (CCL26, CCR4, IL10, IL13, TSLP, TNFRSF4/OX40) and shared downregulation of hair keratins, regardless of atopic background, with variable Th17/Th22 modulation. AA patients with atopy exhibited greater inflammatory tone and Th2‐skewing (IL10, IL13, IL33, CCR4, CCL26). Disease severity correlated significantly with immune and hair keratin biomarkers and with perifollicular cellular infiltrates. Cutaneous OX40/OX40L upregulation was paralleled by increases in circulating OX40+ and OX40L+ leukocytes, regardless of atopic background.ConclusionOur results suggest some atopy‐associated immune differences in AA and highlight the OX40 axis as a potential novel therapeutic target that may broadly benefit AA patients.

中文翻译：

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斑秃表现出跨特应性背景的皮肤和全身 OX40 激活


背景斑秃（AA）是一种慢性、非疤痕性脱发疾病，与严重的生活质量损害和有限的治疗选择相关。最近发现 AA 与特应性有关，并显示出 Th1 和 Th2 驱动的炎症。然而，缺乏特应性和非特应性患者血液和头皮区室的全面分子和细胞特征。方法从 AA 患者中获得病变和非病变头皮活检（ n = 16) 或没有 ( n = 20) 特应性病史，并使用 RNA-seq、RT-PCR 和免疫组织化学对 17 名人口统计学匹配的健康对照进行分析。还对一部分患者的外周血单核细胞 (PBMC) 进行了流式细胞术。使用 |fold-change| 定义差异表达> 1.5 且错误发现率 <0 id=38>IFNG , CXCL9 , CXCL10 , CXCL11 ）和Th2相关产品（覆铜板26 , CCR4 ,白细胞介素10 ,白细胞介素13 , TSLP ,肿瘤坏死因子RSF4 /OX40) 和头发角蛋白的共同下调，无论特应性背景如何，都具有可变的 Th17/Th22 调节。患有特应性的 AA 患者表现出更大的炎症张力和 Th2 偏向（白细胞介素10 ,白细胞介素13 ,白细胞介素33 , CCR4 ,覆铜板26 ）。疾病严重程度与免疫和毛发角蛋白生物标志物以及毛囊周围细胞浸润显着相关。皮肤 OX40/OX40L 上调与循环 OX40 增加同时发生+和OX40L +白细胞，无论特应性背景如何。结论我们的结果表明 AA 中存在一些与特应性相关的免疫差异，并强调 OX40 轴作为潜在的新型治疗靶点，可能使 AA 患者广泛受益。