Submitted by aml95 on Mon, 13/04/2026 - 10:19
Scientists in Cambridge have found evidence linking genetic changes that occur throughout our lives to autoimmune diseases, where cells from the immune system attack healthy cells.
Published in Nature, the pioneering genetic analysis has revealed how somatic mutations – genetic changes that occur throughout our lives – contribute to autoimmune diseases in the thyroid gland.
The research was led by Pantelis Nicola (Wellcome Sanger Institute and a clinical fellow in the Wellcome/Sanger Cambridge PhD for Clinicians programme), Nadia Schoenmakers and John Tadross (Institute of Metabolic Science at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust), working with Andrew Lawson, Iñigo Martincorena (Wellcome Sanger Institute) and colleagues across the Cambridge Biomedical Campus and the NIHR Cambridge Biomedical Research Centre.
The team found that thyroid tissue from patients with autoimmune thyroid disease contain large numbers of B cells (the immune cells that make antibodies), carrying acquired (somatic) mutations in genes which normally function as brakes on the immune response (immune checkpoints).
“Despite their huge impact on people’s health, there is still a lot we don’t know about autoimmune diseases. This work confirms something we’ve long suspected but haven’t had the technology to prove. It’s a key step towards better, more targeted ways to treat people with these conditions, so they can have a better quality of life.”
Dr John Tadross and Dr Nadia Schoenmakers
Using ultra-accurate DNA sequencing alongside spatial and single-cell methods, the researchers found recurrent mutations in key immune checkpoint genes TNFRSF14 and CD274 (which encodes PD-L1). Some of these mutant B-cells were shown to recognise thyroid proteins, suggesting that they contribute directly to the autoimmune attack. The findings provide the clearest evidence yet for a long-standing hypothesis, first proposed by Burnet in the 1950s and expanded in the 1970s, that somatic mutations could allow self-reactive lymphocytes to evade suppression mechanisms.
“Our study suggests that somatic mutations in immune cells may play an important role in autoimmune disease, something researchers have long suspected but lacked the techniques to investigate.”
Dr Andrew Lawson, co-first author at the Wellcome Sanger Institute
"Autoimmune diseases are currently treated by broadly suppressing the immune system, which can leave patients vulnerable to infections as well as a long list of other complications. If these findings are confirmed, they could eventually enable more precise diagnoses and treatments leading to better patient outcomes.”
Dr Pantelis Nicola, co-first author at the Wellcome Sanger Institute
This work suggests that autoimmune disease can occur by somatic evolution, with multiple, small clones of mutant cells acting together over time and identifies new insights into the molecular basis for autoimmune disease and highlights therapeutic targets in pathways that normally keep immune responses under control.
The research team are continuing to build on this work and are now looking to confirm whether these changes can cause illness and exploring their role in other autoimmune conditions.
The work was funded by Wellcome and supported by the NIHR Cambridge Biomedical Research Centre.
News story on Wellcome Sanger Institute website
News story on Cambridge University Hospitals Foundation Trust website
Image credit: Wellcome Sanger Institute
Spatial transcriptomics of thyroid tissue from a donor with autoimmune thyroid disease.
The pink is the structure you would expect to see in healthy thyroid. The green / yellow / orange / blue cells are different types of immune cells that gradually destroy the thyroid until there is essentially nothing left.
