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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This is a summary of: Oda, H. et al. Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency. Nat. Immunol. https://doi.org/10.1038/s41590-024-01817-w (2024).
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Human SHARPIN deficiency is linked to inborn errors of cell death. Nat Immunol 25, 733–734 (2024). https://doi.org/10.1038/s41590-024-01838-5
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DOI: https://doi.org/10.1038/s41590-024-01838-5
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