The Majority of Generalized Pustular Psoriasis without Psoriasis Vulgaris Is Caused by Deficiency of Interleukin-36 Receptor Antagonist
The Majority of Generalized Pustular Psoriasis without Psoriasis Vulgaris Is Caused by Deficiency of Interleukin-36 Receptor Antagonist
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DOI：
10.1038/jid.2013.230
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发表时间：
2013-11-01
影响因子：
6.5
通讯作者：
Akiyama, Masashi
中科院分区：
文献类型：
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作者：
Sugiura, Kazumitsu;Takemoto, Akemi;Akiyama, Masashi
泛发性脓疱性牛皮癣(GPP)是一种罕见的炎症性皮肤病，可危及生命。最近有报道称家族性GPP是由IL36RN纯合子或复合杂合子突变引起的。然而，大多数GPP病例是散发性的，IL36RN突变是否是散发性GPP的致病/易感因素仍有争议。在这项研究中，我们在日本人群中的两组GPP患者中寻找IL36RN突变：无寻常型银屑病(PV)的GPP和有PV的GPP。对11例GPP无PV(单纯GPP)和20例GPP合并PV(GPP伴PV)进行分析。令人惊讶的是，11例GPP中有9例存在IL36RN纯合子或复合杂合子突变。相比之下，20例GPP合并PV中只有2例存在IL36RN复合杂合性突变。具有IL36RN复合杂合子突变的两例GPP合并PV是兄弟姐妹，两例都有PV易感的HLA-A*0206。我们确定GPP单独是GPP的一个不同的亚型，在病因学上与GPP合并PV区分开来，并且大多数GPP单独是由于IL36RN突变导致的白介素36受体拮抗剂缺乏所致。
Generalized pustular psoriasis (GPP) is a rare inflammatory skin disease that can be life-threatening. Recently, it has been reported that familial GPP is caused by homozygous or compound heterozygous mutations of IL36RN. However, the majority of GPP cases are sporadic and it is controversial whether IL36RN mutations are a causative/predisposing factor for sporadic GPP. We searched for IL36RN mutations in two groups of GPP patients in the Japanese population in this study: GPP without psoriasis vulgaris (PV), and GPP with PV. Eleven cases of GPP without PV (GPP alone) and 20 cases of GPP accompanied by PV (GPP with PV) were analyzed. Surprisingly, 9 out of 11 cases of GPP alone had homozygous or compound heterozygous mutations in IL36RN. In contrast, only 2 of 20 cases of GPP with PV had compound heterozygous mutations in IL36RN. The two cases of GPP with PV who had compound heterozygous mutations in IL36RN are siblings, and both cases had PV-susceptible HLA-A*0206. We determined that GPP alone is a distinct subtype of GPP and is etiologically distinguished from GPP with PV, and that the majority of GPP alone is caused by deficiency of the interleukin-36 receptor antagonist due to IL36RN mutations.