Certain patients with the autoimmune disease scleroderma who have autoantibodies specific for RNA polymerase III subunit (RPC1; encoded by POLR3A) develop cancer around the same time as the autoimmune disease. This study found that tumours from six of eight scleroderma patients with RPC1-specific autoantibodies had genetic alterations affecting the POLR3A locus, whereas no POLR3A alterations were detected in tumours from eight scleroderma patients with other autoantibodies. CD4+ T cells specific for the mutant RPC1 peptides were identified in two of the three patients analysed. These T cells did not cross-react with the native RPC1 protein but the autoantibodies in these patients recognized both native and mutant RPC1. So, the data suggest that the mutant RPC1 generated in tumour cells acts as an immunogen for CD4+ T cells; these cells may help to control the cancer through immunoediting, but may also promote a cross-reactive humoral immune response that triggers scleroderma.
References
Joseph, C. G. et al. Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science 343, 152–157 (2014)
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Leavy, O. A link between autoimmunity and cancer?. Nat Rev Immunol 14, 67 (2014). https://doi.org/10.1038/nri3620
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DOI: https://doi.org/10.1038/nri3620