- Accumulation of somatic mutations within cells is known to
contribute to the development of cancer by causing their unregulated
- Current study suggests that a similar mechanism of somatic
mutations in mature effector T-cells might also be associated with the
development of autoimmunity.
in the genes encoding immune function have been detected in CD8+ T-cells in
rheumatoid arthritis patients in a study undertaken by the
University of Helsinki and the Helsinki University Central Hospital, suggesting
that such mutations might be contributing to the evolution of autoimmune
diseases such as rheumatoid arthritis.
The findings of the study were published
in the Nature Communications
‘Mutations in CD8+ve T-cells might lead to dysregulation of the inflammatory process causing autoimmune diseases like rheumatoid arthritis.’
Lymphocyte (LGL) Leukemia and Rheumatoid Arthritis Connection - The Basis of the Study
- Rheumatoid arthritis has often been found to
occur in LGL leukemia, a type of lymphoproliferative disorder.
- Studies have shown that expanded
clones of CD8+ve T-cells in LGL leukemia show STAT3 (Signal transducer and activator of transcription 3) gene
- The incidence of rheumatoid
arthritis (an autoimmune disease) in LGL leukemia patients with STAT3 gene
mutation was 43% compared to only 6% of patients who did not have the
- This association between LGL
leukemia and rheumatoid arthritis raises the possibility that CD8+ve
T-cell clones harboring somatic mutations could contribute to autoimmune disease.
Taking a cue from the above observations,
the research team hoped to pursue the matter further and investigate whether persons with only autoimmune disease (eg., rheumatoid arthritis) in the absence of
any lymphoproliferative cancer could also show somatic mutations in their
Testing for Mutations in
Rheumatoid Arthritis Patients
- The study included 80 newly
diagnosed rheumatoid arthritis patients and 20 healthy controls.
- Blood samples of both the patients
and the controls were analyzed for the presence of
mutations by employing the latest sequencing techniques.
- 20 percent of the patients showed
somatic mutations of genes affecting immune function and cell
proliferation in contrast to just 1 among the control group.
- All the mutations were found in
cytotoxic CD8+ve clonal T-cells associated with rheumatoid arthritis;
the CD4+ve helper T-cells did not demonstrate any mutations.
"This indicates that mutations are
formed only in mature T cells, not at the stem cell level," say BM Paula
Savola and PhD Tiina Kelkka, the main authors of the article. "If
mutations were formed at the earlier differentiation stage, they would have
been present in CD8+ T cells and CD4+ helper cells expressing other T cell
receptor types as well."
Scope of the Study and
- The mutations were permanent i.e.
the same mutations and identical clonal T-cells were found in the patients
several years after the initial finding.
- The significance of these findings
is not yet clear. More
research is required to validate the role of mutations in effector T-cells
and the mechanisms involved in the development of rheumatoid arthritis or
similar autoimmune disease. Nevertheless, this study has demonstrated a
connection between somatic mutations and a non-malignant autoimmune
"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
- The study findings suggest that chronic inflammatory conditions such
as rheumatoid arthritis may predispose to the accumulation of
somatic mutations. In future, the study team plans to analyze similar mutations in other chronic
"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," says Mustjoki.
In conclusion, the idea of mutations
leading to autoimmunity is indeed novel, and only time will tell whether this hypothesis proves to be a game-changer in the way autoimmune diseases are approached in the future.
Mutations in Clonally Expanded Cytotoxic Lymphocytes in Patients with Newly Diagnosed Rheumatoid Arthritis - (http://acrabstracts.org/abstract/somatic-mutations-in-clonally-expanded-cytotoxic-lymphocytes-in-patients-with-