Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
Department of Dermatology, Fujita Health University, Toyoake, Japan.
J Dermatol. 2023 Dec;50(12):1608-1613. doi: 10.1111/1346-8138.16914. Epub 2023 Jul 31.
It has recently been revealed that mutation of the IL36RN gene contributes to the development of generalized pustular psoriasis (GPP). The IL36RN gene encodes interleukin (IL)-36 receptor antagonist (IL-36Ra), which has antagonistic roles against IL-36α, -36β, and -36γ. Previously, sanger sequencing performed in 62 Chinese GPP patients to identify IL36RN mutations revealed a new variant, c.245C>T (p.Pro82Leu), in a single heterozygous state in a patient with adult-onset GPP with psoriasis vulgaris. Since this p.Pro82Leu variant was not found in the psoriasis vulgaris or control groups in their study, they speculated that this variant might lead to exacerbated inflammatory responses. Meanwhile, Sorting Intolerant From Tolerant and PolyPhen-2, pathogenicity prediction tools, predict this variant as tolerated and benign. To date, its pathogenicity is unknown. We experienced a patient with GPP harboring the p.Pro82Leu variant, and investigated mRNA and protein expressions of IL-36Ra. Polymerase chain reaction conducted on hair follicle samples obtained from the scalp of the patient with GPP harboring the p.Pro82Leu using primers to detect mRNA of exons 2 and 5 in IL36RN demonstrated mRNA expression of IL36RN. Immunohistochemical staining revealed IL-36Ra expression in the keratinocytes of the patient with GPP harboring the p.Pro82Leu as in those of a GPP patient without the mutation (positive control). Furthermore, quantitative analysis of the immunofluorescent staining by ImageJ revealed that the expression level of IL-36Ra in the keratinocytes of the patient with GPP harboring p.Pro82Leu was higher than that in the healthy control and not lower than that in the GPP patients without the mutation. Our results indicate no aberrant splicing in this variant. In addition, according to the 1000 Genomes Project, this variant could be a founder mutation. Considering these factors together, this variant is unlikely to be associated with the development of GPP.
最近的研究表明，IL36RN 基因突变导致泛发性脓疱型银屑病（GPP）的发生。IL36RN 基因编码白细胞介素（IL）-36 受体拮抗剂（IL-36Ra），其对 IL-36α、-36β 和 -36γ 具有拮抗作用。先前，研究人员对 62 名中国 GPP 患者进行了 Sanger 测序以鉴定 IL36RN 突变，在一名患有寻常型银屑病的成人发病 GPP 患者中发现了一个新的单杂合状态的变体 c.245C>T（p.Pro82Leu）。由于在他们的研究中未在寻常型银屑病或对照组中发现该 p.Pro82Leu 变体，他们推测该变体可能导致炎症反应加剧。同时，Sorting Intolerant From Tolerant 和 PolyPhen-2 这两种致病性预测工具预测该变体是耐受的和良性的。迄今为止，其致病性尚不清楚。我们遇到了一名 GPP 患者，该患者携带 p.Pro82Leu 变体，并研究了 IL-36Ra 的 mRNA 和蛋白表达。使用 IL36RN 外显子 2 和 5 的引物对来自 GPP 患者头皮的毛囊样本进行聚合酶链反应，该患者携带 p.Pro82Leu 变体，证明了 IL36RN 的 mRNA 表达。免疫组织化学染色显示 p.Pro82Leu 变体 GPP 患者的角质形成细胞中存在 IL-36Ra 表达，与无突变的 GPP 患者（阳性对照）相似。此外，使用 ImageJ 对免疫荧光染色进行定量分析表明，p.Pro82Leu 变体 GPP 患者的角质形成细胞中 IL-36Ra 的表达水平高于健康对照组，且不低于无突变的 GPP 患者。我们的结果表明该变体没有异常剪接。此外，根据 1000 基因组计划，该变体可能是一个创始突变。综合考虑这些因素，该变体不太可能与 GPP 的发生有关。
