25 November 2020
Pinpointing a genetic defect linked to immunodeficiency
Published online 22 July 2018
Defects in RIPK1, a protein implicated in inflammation and cell death, can lead to chronic immune system disorders.
Scientists home in on mutations that cause primary immunodeficiencies (PIDs), a group of chronic genetic disorders, which bring recurrent or persistent infections due to a compromised immune system.
To investigate how PIDs work, they sequenced the genomes of four patients suffering normal symptoms such as viral and bacterial infections, as well as inflammation of the bowel and joints. They described their findings in a new study in Science1.
The team, which included researchers from the King Saud bin Abdulaziz University for Health Sciences, and Albaha University in Saudi Arabia, has pinpointed rare mutations in the Receptor Interacting Serine/Threonine Kinase 1 or RIPK1. This gene codes for an enzyme that is essential in mediating cellular functions that eventually stimulate the immune cells responsible for fighting infections and mitigating the body’s reaction to inflammation.
The mutations diminished RIPK1 ultimately resulting in PIDs.
"Although, RIPK1 had been extensively studied in animal models, we uncover, for the first time, its role in humans,” says the study’s lead investigator Sergey Nejentsev at the Department of Medicine of the University of Cambridge, UK. While RIPK1 deficiency in mice typically leads to multiple system defects, the effect of its deficiency in humans seems to be nearly exclusive to the immune system.
According to Nejentsev, based on their findings, transplantation of blood stem cells “can be an effective treatment for [PIDs] patients if performed early in life.”
- Cuchet-Lourenç C. et al. Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. Science. http://dx.doi.org/10.1126/science.aar2641 (2018).