Abstract
Autoimmune myopathies (myositides) are strongly associated with malignancy. The link between myositis and cancer, originally noticed by Bohan and Peter in their classification in 1975 (1), has been evidenced by large population-based cohort studies and a recent meta-analysis. The numerous reports of cases in which the clinical course of myositis reflects that of cancer and the short delay between myositis and cancer onset support the notion that myositis may be an authentic paraneoplastic disorder. Thus, cancer-associated myositis raises the question of cancer as a cause rather than a consequence of autoimmunity. Among myositides, dermatomyositis and more recently, although to a lesser extent, immune-mediated necrotizing myopathies are the most documented forms associated with cancer. Interestingly, the current diagnostic approach for myositis is based on the identification of specific antibodies where each antibody determines specific clinical features and outcomes. Recent findings have shown that the autoantibodies anti-TIF1γ, anti-NXP2 and anti-HMGCR are associated with cancers in the course of myositis. Herein, we highlight the fact that the targets of these three autoantibodies involve cellular pathways that intervene in tumor promotion and we discuss the role of cancer mutations as autoimmunity triggers in adult myositis.
Highlights
The link between autoimmunity and cancer has become a topic of unceasing interest over the past decade
One important question here recalls the old eggand-chicken dilemma: is the autoimmune background in autoimmune diseases (AID) a seedbed for cancer development or, alternatively, may cancer cause autoimmunity?
The immunogenic peptides generated by POLR3 gene mutations induce a POL3-specific CD4+ T cell response with production of specific antibodies that secondarily target wild-type POL3 by epitope spreading [11]. This present review focuses on the forms of myositides, i.e., dermatomyositis (DM) and immune-mediated necrotizing myopathies (IMNMs) which have been identified as associated with cancer and represent a paradigm of cancerassociated AID
Summary
The link between autoimmunity and cancer has become a topic of unceasing interest over the past decade. It is increasingly evident that the risk of cancer is augmented in patients affected by several types of autoimmune diseases (AID), the nature of the interplay between autoimmunity and cancer remains elusive [2,3,4]. One important question here recalls the old eggand-chicken dilemma: is the autoimmune background in AID a seedbed for cancer development or, alternatively, may cancer cause autoimmunity?. Rheumatic AID such as systemic lupus erythematosus, rheumatoid arthritis, or Sjögren syndrome promote cancer development after several years of chronic inflammation and exposure to immunosuppressive drugs [2, 5, 6]. The risk of cancer cannot only be ascribed to the sole autoimmune status and presumably to iatrogenic immunosuppression
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