Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies.
Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting Follicular Adnexal Structures: A Hypothesis Based on Molecular and Clinicopathologic Studies.
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经典的溃疡性脓疱性坏疽是一种T细胞介导的靶向卵泡附件结构的疾病：基于分子和临床病理学研究的假设。
DOI：
10.3389/fimmu.2017.01980
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发表时间：
2017
影响因子：
7.3
通讯作者：
Maverakis E
中科院分区：
文献类型：
--
作者：
Wang EA;Steel A;Luxardi G;Mitra A;Patel F;Cheng MY;Wilken R;Kao J;de Ga K;Sultani H;Merleev AA;Marusina AI;Brassard A;Fung MA;Konia T;Shimoda M;Maverakis E
坏疽性脓皮病（PG）是一种使人衰弱的溃疡性皮肤病，是炎症性肠病和类风湿性关节炎患者中最常见的相关疾病之一。虽然PG被归类为嗜中性皮肤病，但其病理生理学知之甚少。使用从患者报告的病史、免疫组织化学和基因表达分析中获得的数据来制定关于PG病理生理学的假设。10名PG患者参与并回答了有关新溃疡形成的问题。从4名患者中获得愈合的先前溃疡和邻近正常皮肤的皮肤活检用于免疫组织化学。来自健康患者和盘状狼疮患者的瘢痕被用作额外的对照。采用免疫组化和实时定量PCR基因表达分析对新发PG丘疹进行分析。所有PG患者均报告既往溃疡愈合部位难以再溃疡。同时活检愈合和未涉及的皮肤引发溃疡，只有在后者。在免疫组织化学上，愈合的PG瘢痕显示毛囊皮脂腺单位完全丧失，这在正常皮肤中存在，在对照瘢痕和盘状瘢痕中程度较轻。早期PG丘疹显示血管周围和毛囊皮脂腺周围T细胞浸润，而不是中性粒细胞。这些早期炎症事件主要由CXCL 9、CXCL 10、CXCL 11、IL-8、IL-17、IFNG和IL-36 G以及与Th 1表型一致的转录因子的基因表达增加所主导。样本量小是主要限制。我们提出的假设，PG是一个T细胞的反应，导致破坏的毛囊皮脂腺单位。
Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that is one of the most common associated diseases seen in patients with inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as a neutrophilic dermatosis, its pathophysiology is poorly understood. Use data obtained from patient-reported histories, immunohistochemistry, and gene expression analysis to formulate a hypothesis on PG pathophysiology. Ten PG patients participated and answered questions about new ulcer formation. Skin biopsies of healed prior ulcers and adjacent normal skin were obtained from four patients for immunohistochemistry. Scars from healthy patients and patients with discoid lupus were used as additional controls. New onset PG papules were analyzed using immunohistochemistry and gene expression analysis via quantitative real-time PCR. All PG patients reported that healed sites of previous ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and uninvolved skin triggered ulceration only in the latter. On immunohistochemistry, healed PG scars showed complete loss of pilosebaceous units, which were present in normal skin, and to a lesser extent in control scars, and discoid scars. Early PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather than neutrophils. These early inflammatory events were dominated by increased gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and transcription factors consistent with Th1 phenotype. Small sample size was the main limitation. We put forth the hypothesis that PG is a T cell response resulting in the destruction of pilosebaceous units.