Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases.
Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases.
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DOI：
10.1097/md.0000000000000187
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发表时间：
2014-12
期刊：
影响因子：
1.6
通讯作者：
Cugno M
中科院分区：
文献类型：
--
作者：
Marzano AV;Ceccherini I;Gattorno M;Fanoni D;Caroli F;Rusmini M;Grossi A;De Simone C;Borghi OM;Meroni PL;Crosti C;Cugno M
坏疽性脓疡、痤疮和化脓性汗腺炎（PASH）的关联最近被描述，并被认为是自身炎症综合征谱内的一个新实体，其特征在于无菌炎症的反复发作，没有循环自身抗体和自身反应性T细胞。我们对5例PASH综合征患者进行了观察性研究，分析了他们的临床特征、已知与自身炎症性疾病（AIDS）有关的10个基因的遗传谱以及皮损和血清中细胞因子的表达模式。PASH患者皮肤组织中IL-1 β及其受体I和II的表达显著高于对照组（P分别为0.028、0.047和0.050）。 在PASH患者中，趋化因子IL-8（P = 0.004）、C-X-C基序配体（CXCL）1/2/3（P = 0.028）、CXCL 16（P = 0.008）和调节活化、正常T细胞表达和分泌（RANTES）（P = 0.005）均过表达。 Fas/Fas配体和分化簇（CD）40/CD 40配体系统也过表达（Fas P = 0.016，Fas配体P=0.006，CD 40 P =0.005， CD 40配体P=0.004），导致组织损伤和炎症。 在外周血中，主要促炎细胞因子，即IL-1β、肿瘤坏死因子-α和IL-17的血清水平在正常范围内，表明在PASH综合征中，炎症过程主要局限于皮肤。我们的5例PASH患者中有4例出现了典型的艾滋病遗传改变，包括炎症性肠病，唯一一例缺乏遗传改变的患者有临床明显的克罗恩病。总之，细胞因子/趋化因子和放大炎症网络的分子的过表达，沿着遗传变化，支持PASH综合征起源于自身炎症的观点。
The association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) has recently been described and suggested to be a new entity within the spectrum of autoinflammatory syndromes, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T-cells. We conducted an observational study on 5 patients with PASH syndrome, analyzing their clinical features, genetic profile of 10 genes already known to be involved in autoinflammatory diseases (AIDs), and cytokine expression pattern both in lesional skin and serum. In tissue skin samples, the expressions of interleukin (IL)-1β and its receptors I and II were significantly higher in PASH (P = 0.028, 0.047, and 0.050, respectively) than in controls. In PASH patients, chemokines such as IL-8 (P = 0.004), C-X-C motif ligand (CXCL) 1/2/3 (P = 0.028), CXCL 16 (P = 0.008), and regulated on activation, normal T cell expressed and secreted (RANTES) (P = 0.005) were overexpressed. Fas/Fas ligand and cluster of differentiation (CD)40/CD40 ligand systems were also overexpressed (P = 0.016 for Fas, P = 0.006 for Fas ligand, P = 0.005 for CD40, and P = 0.004 for CD40 ligand), contributing to tissue damage and inflammation. In peripheral blood, serum levels of the main proinflammatory cytokines, that is, IL-1β, tumor necrosis factor-α, and IL-17, were within the normal range, suggesting that in PASH syndrome, the inflammatory process is mainly localized into the skin. Four out of our 5 PASH patients presented genetic alterations typical of well-known AIDs, including inflammatory bowel diseases, and the only patient lacking genetic changes had clinically evident Crohn disease. In conclusion, overexpression of cytokines/chemokines and molecules amplifying the inflammatory network, along with the genetic changes, supports the view that PASH syndrome is autoinflammatory in origin.