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Human SHARPIN deficiency is linked to inborn errors of cell death

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.

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Fig. 1: Clinical and immunological characterizations of sharpenia.


  1. Manthiram, K. et al. The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat. Immunol. 18, 832–842 (2017). A review article that discusses the genetic and molecular architecture of monogenic autoinflammatory diseases.

    Article  CAS  PubMed  Google Scholar 

  2. Lalaoui, N. et al. Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease. Nature 577, 103–108 (2020). This paper reports a human disorder caused by cleavage-resistant mutations in RIPK1 that lead to cell death-induced autoinflammation.

    Article  CAS  PubMed  Google Scholar 

  3. Peltzer, N. & Walczak, H. Cell death and inflammation — a vital but dangerous liaison. Trends Immunol. 40, 387–402 (2019). A review article that discusses the molecular mechanisms of how LUBAC regulates immune and cell death signaling.

    Article  CAS  PubMed  Google Scholar 

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This is a summary of: Oda, H. et al. Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency. Nat. Immunol. (2024).

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Human SHARPIN deficiency is linked to inborn errors of cell death. Nat Immunol 25, 733–734 (2024).

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