Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)
Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)
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DOI：
10.1111/bjd.15226
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发表时间：
2017-06-01
影响因子：
10.3
通讯作者：
Cugno, M.
中科院分区：
文献类型：
--
作者：
Marzano, A. V.;Damiani, G.;Cugno, M.
背景坏疽脓皮病(PG)是一种罕见的皮肤病，临床上以边界破坏的溃疡为特征，组织学上以富含中性粒细胞的浸润物为特征。目的探讨PG与自身炎症相关的特殊遗传背景。方法对13例PG患者和7例PASH(坏疽脓皮病、痤疮、化脓性汗腺炎)患者的细胞因子谱和参与自身炎症的基因进行检测。结果皮肤组织中IL-1β及其受体、IL-17及其受体、IL-1β、IL-1β、IL-17、IL-1β、IL-1β、IL-17、IL-1β、IL-1β及其受体、IL-17及其受体在13例PG患者和7例PASH(坏疽脓皮病、痤疮、化脓性汗腺炎)患者中的表达。肿瘤坏死因子-a及其受体在PG(P=0.001)和PASH(P<；0.001)，而不是对照组。趋化因子IL-8、趋化因子(C-X-C基序)配体1/2/3、趋化因子(C-X-C基序)配体16和RANTES(调节活化、正常T细胞表达和分泌)也过表达。4例PG和PASH自身炎症基因MEFV、NLRP3、NLRP12、NOD2、LPIN2和PSTPIP1均发生突变。结论细胞因子/趋化因子的过度表达和基因改变支持PG及其综合征PASH是一种多基因自炎的假说。
Background Pyoderma gangrenosum (PG) is a rare skin disease characterized clinically by ulcers with undermined borders, and histologically by neutrophil-rich infiltrates. PG may occur alone, in syndromic forms or associated with systemic diseases, such as inflammatory bowel disease and haematological or rheumatological disorders.Objectives To determine a specific genetic background related to autoinflammation for PG.Methods We assessed autoinflammation by evaluating the cytokine profile and genes involved in classic autoinflammatory diseases in 13 patients with PG and in seven patients with the syndromic form, known as PASH (pyoderma gangrenosum, acne and suppurative hidradenitis).Results In skin samples, the expression of interleukin (IL)-1 beta and its receptors, IL-17 and its receptor, and tumour necrosis factor-a and its receptors were significantly higher in both PG (P = 0.001) and in PASH (P < 0.001) than in controls. The chemokines IL-8; chemokine (C-X-C motif) ligand 1/2/3; chemokine (C-X-C motif) ligand 16; and RANTES (regulated on activation, normal T-cell-expressed and secreted) were also overexpressed. Cases of PG and PASH showed mutations in the autoinflammatory genes MEFV, NLRP3, NLRP12, NOD2, LPIN2 and PSTPIP1.Conclusions Overexpression of cytokines/chemokines, along with genetic changes, supports the hypothesis that PG and its syndromic form, PASH, are a spectrum of polygenic autoinflammatory conditions.