A new study has identified for the first time how a common process in cancer might be involved in the development of autoimmune diseases.

Researchers at the University of Helsinki and the Institute for Molecular Medicine Finland have found that the accumulation of mutations in mature immune cells could drive rheumatoid arthritis in a similar way to how somatic mutations drive cancer. This phenomenon has been extensively studied in tumors, but this study is the first to investigate it in other diseases.

The results, published today in Nature Communications, revealed 30 mutations in CD8+ cytotoxic T cells of 5 out of 25 patients with rheumatoid arthritis, versus a single mutation in one out of 20 healthy patients. The mutations were found in genes linked with the regulation of immunity and cell proliferation, and the clones of those cells with mutations appeared in much larger quantities that T cell clones without the mutations.

Interestingly, all the mutations were found in cytotoxic CD8+ T cells, and none in helper CD4+ T cells. Given both cell types have a common origin, it was determined that the mutations appeared in mature cells and were not related to genetic defects in the stem cells that produce new immune cells every day.

Helsinki University Cancer Arthritis

Counterintuitively, none of the mutations identified were found in other 82 rheumatoid arthritis patients, indicating that rather than being driven by any specific genes, the process would depend on the accumulation of nonspecific mutations.

The prevalence of these types of mutations in hematopoietic cells increases with age, a process that has been extensively linked to an increased risk of cancer, and particularly blood cancer. These results indicate that the same process could also be behind a higher risk of suffering from an autoimmune disease.

For now, there is no certainty on how these mutations affect the regulation of chronic inflammations,” says Professor Satu Mustjoki, one of the project’s leaders. “They may be, for lack of a better word, ‘genomic scars’ formed as a result of the activation of the immune defense system. In any case, this research project revealed a new connection on the molecular level between autoimmune diseases and cancer, which brings us one step closer to understanding these diseases.

After this first step, further studies with larger patients cohorts are definitely needed to confirm the results and gain a deeper insight into the mechanisms by which these mutations result in autoimmune disease. As Mustjoki stated, his group is planning to continue investigating the phenomenon in several inflammatory conditions.


Images via nobeastsofierce / Shutterstock; P Savola et al. Nature Communications 8, 15869 (2017)

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