| Title: |
Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. |
| Authors: |
Cuchet-Lourenço, D; Eletto, D; Wu, C; Plagnol, V; Papapietro, O; Curtis, J; Ceron-Gutierrez, L; Bacon, CM; Hackett, S; Alsaleem, B; Maes, M; Gaspar, M; Alisaac, A; Goss, E; AlIdrissi, E; Siegmund, D; Wajant, H; Kumararatne, D; AlZahrani, MS; Arkwright, PD; Abinun, M; Doffinger, R; Nejentsev, S |
| Source: |
Science , 361 (6404) pp. 810-813. (2018) |
| Publication Year: |
2018 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Alleles; Arthritis; Cytokines; Female; Fibroblasts; Humans; Inflammatory Bowel Diseases; Lymphopenia; Male; Mitogen-Activated Protein Kinases; Pedigree; Receptor-Interacting Protein Serine-Threonine Kinases; Severe Combined Immunodeficiency |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10062945/1/Manuscript_with_figures_revised.pdf; https://discovery.ucl.ac.uk/id/eprint/10062945/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10062945/1/Manuscript_with_figures_revised.pdf; https://discovery.ucl.ac.uk/id/eprint/10062945/ |
| Rights: |
open |
| Accession Number: |
edsbas.60438084 |
| Database: |
BASE |