Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation

Delphine Cuchet-Lourenço, Davide Eletto, Changxin Wu, Vincent Plagnol, Olivier Papapietro, James Curtis, Lourdes Ceron-Gutierrez, Chris M Bacon, Scott Hackett, Badr Alsaleem, Mailis Maes, Miguel Gaspar, Ali Alisaac, Emma Goss, Eman AlIdrissi, Daniela Siegmund, Harald Wajant, Dinakantha Kumararatne, Mofareh S AlZahrani, Peter D ArkwrightMario Abinun, Rainer Doffinger, Sergey Nejentsev

Research output: Contribution to journalArticleAcademicpeer-review

167 Citations (Scopus)


RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.

Original languageEnglish
Pages (from-to)810-813
Number of pages4
Issue number6404
Publication statusPublished - 24 Aug 2018
Externally publishedYes


  • Alleles
  • Arthritis/genetics
  • Cytokines/metabolism
  • Female
  • Fibroblasts/metabolism
  • Humans
  • Inflammatory Bowel Diseases/genetics
  • Lymphopenia/genetics
  • Male
  • Mitogen-Activated Protein Kinases/metabolism
  • Pedigree
  • Receptor-Interacting Protein Serine-Threonine Kinases/genetics
  • Severe Combined Immunodeficiency/genetics

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