We report two patients with biallelic SHARPIN deficiency, which manifests with autoinflammation and B cell immunodeficiency and is phenotypically distinct from Sharpin deficiency in mice. In one patient, there was a significant shift from pro-survival signaling to cell-death signaling in fibroblasts and lymphoblasts induced by members of the TNF cytokine superfamily, accounting for the autoinflammation and immunodeficiency. Targeted therapy with TNF inhibitors had a dramatic beneficial effect.

中文翻译：

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人类 SHARPIN 缺陷与先天性细胞死亡错误有关

我们报告了两名患有双等位基因 SHARPIN 缺陷的患者，其表现为自身炎症和 B 细胞免疫缺陷，并且在表型上与小鼠的 Sharpin 缺陷不同。在一名患者中，TNF 细胞因子超家族成员诱导的成纤维细胞和淋巴母细胞中存在从促生存信号传导到细胞死亡信号传导的显着转变，这是自身炎症和免疫缺陷的原因。 TNF 抑制剂的靶向治疗具有显着的有益效果。