Connection Between Autoimmune Diseases, Cancer Found on a Molecular Level

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Accumulation of gene mutations occurs in some patients with rheumatoid arthritis, study finds.

Scientists have found similarities among mutations that accumulate within cells that cause cancer to develop and those that occur in some patients with rheumatoid arthritis (RA).

In a study published in Nature Communications, investigators found that the accumulation of somatic mutations in expanded CD8+ T cells may have pathogenics significant for RA and other autoimmune diseases.

“It may be possible that these mutations affect the regulation of the inflammatory process,” author Satu Mustjoki, told News-Medical.

The investigators sought to determine whether T cells in patients with non-malignant autoimmune disorders and without known lymphoproliferation harbor somatic mutations.

Blood samples were collected from 82 untreated, newly diagnosed RA patients and 20 healthy controls.

Using flow cytometry screening, the results of the study showed an increase clonality in CD8+ T cells compared with CD4+ T cells. Deep TCRB-sequencing was also utilized, revealing that the clonality of CD8+ T cells did not significant differ in patients with RA compared with age-matched healthy controls, according to the study. However, clonality increased with age in patients but not in healthy controls.

One-fifth of patients with RA had mutations, all of which were located in cytotoxic CD8+ T cells. No mutations were found in CD4+T cells, according to the study.

Enlarged T cell clones were also found in all participants with RA with somatic mutations. Upon further investigation, the investigators found that the mutations were limited to the enlarged cell clones.

“This indicated that mutations are formed only in mature T cells, not at the stem cell level,” authors BM Paula Savola and Tiina Kelkka, PhD, told News-Medical.

Several years later, the identical clones and somatic mutations remained in the patients’ white blood cells, indicating their permanence.

“For now, there is no certainty on how these mutations affect the regulation of chronic inflammations,” Mustjoki told News-Medical. “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 disease and cancer, which brings us one step closer to understanding these diseases.

“In the future, we intend to study the prevalence of this phenomenon in other inflammatory conditions and the practical significance of these mutations as regulators of inflammatory reactions.”

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