On Apr. 14, 2026, researchers from the Wellcome Sanger Institute, Cambridge University Hospitals NHS Foundation Trust (CUH), the University of Cambridge, and their collaborators announced that new research suggests that autoimmune diseases may be driven by DNA mutations in immune cells that remove the natural brakes on the immune system. It reveals a previously hidden role for somatic mutations — DNA changes acquired throughout life — in diseases beyond cancer. The team used a series of cutting-edge techniques to identify previously unseen changes in DNA that may contribute to thyroid autoimmunity, where the immune system attacks the thyroid gland.

Reported in Nature, the findings could change the way we think about autoimmune diseases and provide a potential path towards precision medicine. Autoimmune disease is an umbrella term for a long list of diseases in which the immune system mistakenly attacks the body’s own healthy cells, believing they are foreign pathogens. Examples include rheumatoid arthritis, multiple sclerosis, lupus and type 1 diabetes. Autoimmune diseases affect five to 10 per cent of the global population, however their molecular basis remains poorly understood.

Somatic mutations are changes in DNA that occur in our cells over time and are not inherited. They are responsible for cancer and have long been speculated to contribute to other diseases. But studying these mutations outside of cancer has been technically challenging. Recent advances in DNA sequencing methods, including some spearheaded by the Sanger Institute over the last decade, now make their study across diseases possible.

Since the 1950s, some scientists have speculated that somatic mutations in lymphocytes – types of white blood cells, including B cells – could lift the brakes on the immune system, allowing it to attack the body’s own tissues during autoimmunity. Unlike cancer, which usually starts when a single mutated cell multiplies uncontrollably into a tumour, autoimmune diseases are driven by many different groups of immune cells acting together. This complexity has made the search for mutations in lymphocytes difficult.

In a new study, researchers at the Sanger Institute and their collaborators tested this idea, using a series of cutting-edge methods to investigate whether somatic mutations contribute to diseases beyond cancer. The researchers studied thyroid autoimmune disease, including samples from consenting patients with Hashimoto’s and Graves’ disease, which are leading causes of thyroid dysfunction in the population. The researchers used several advanced DNA analysis techniques. Firstly, they used a method called NanoSeq, which they recently developed and allows detection of rare mutations invisible to traditional DNA sequencing methods, to look for genetic changes that may drive the disease. They found that many B cells had developed inactivating mutations in key genes that normally control the immune system.

Next, using additional methods that look at the DNA of individual cells and microscopic areas of tissue, the researchers found that many B cells in each patient carried several mutations in key genes. Two critical immune-checkpoint genes, TNFRSF14 and CD274 (or PDL1), were often lost independently in multiple clones of mutated B cells in each patient. Some of these clones had even acquired as many as six driver mutations over many years, silently building up changes in DNA before symptoms appeared, a highly unexpected observation outside of cancer. Importantly, artificial inactivation of these genes, in experimental studies or during cancer immunotherapy, is known to cause thyroid autoimmunity. The researchers have now found frequent mutations in these genes occurring in autoimmune patients.

This research reveals a hidden world of somatic evolution in B cells during autoimmunity and provides the strongest evidence to date for an important role of somatic mutations in a common autoimmune disease. However, further research is required to confirm if these mutations are the root cause of autoimmune disease or perhaps just contribute to its exacerbation over time. The research team has also started to see similar results in other autoimmune diseases, but these are preliminary findings and require more investigation.