Several rare immune disorders are caused by mutations in the patient's DNA. The University of Surrey and its collaborators found that targeting the mutated pathways with new drugs offers new hope for people suffering from rare conditions such as immunodeficiencies.
The multidisciplinary team looked at a genetic mutation called biallelic PI4KA, which impacts B cells in the body (the ones that produce antibodies) and is important for helping our immune system fight off infections.
These mutations disrupt the B cells in these patients, making it hard for the cells to develop and function properly. The team suggests using new drugs called mTOR inhibitors to treat these rare conditions.
We hope our research brings hope to people suffering from these rare conditions. Using our multi-omics, big-data integration approach, we are working to better understand how these rare mutations impact the immune system by ultimately disrupting metabolic functions, thus affecting how cells use energy."
Dr. Matteo Barberis, lead author of the study and Reader in Systems Biology from the University of Surrey
The Surrey team used advanced "multi-omics" techniques to understand the effects of the PI4KA mutation on B cells. By examining the genetic activity, protein composition, and metabolic functions of these cells, they identified how the mutation leads to critical disruptions in cell energy production and immune cell signalling. The team's detailed biochemical analysis allowed them to pinpoint the exact pathways affected, offering valuable insights into potential therapeutic targets for restoring normal B cell function.
Dr. Matteo Barberis added:
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"These mutations only impact a small number of people in the world; however, what we have learned could have broader implications for understanding how immune cells function in other diseases. We are now looking at how we can translate our study to potential clinical solutions, hoping to move towards trials that could bring new therapies to patients in the near future."
The study has been published in the Journal of Clinical Immunology.
University of Surrey
Journal reference:
Saettini, F., et al. (2024) Biallelic PI4KA Mutations Disrupt B-Cell Metabolism and Cause B-Cell Lymphopenia and Hypogammaglobulinemia. Journal of Clinical Immunology. doi.org/10.1007/s10875-024-01793-8.