Dermatomyositis and Immune-Mediated Necrotizing Myopathies: A Window on Autoimmunity and Cancer

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.

The IgG2 Isotype of Anti–Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis

“…The parallel evolution of anti‐TIF1γ autoantibodies and cancer corroborates the potential role of tumors to promote an anti‐TIF1γ response that secondarily deviates towards muscle and skin . As with anti‐Hu–positive autoantibody in encephalitis or anti‐POL3–positive autoantibodies in systemic sclerosis , it is tempting to speculate that a tumor may harbor ectopically expressed or mutated TIF1γ antigens, leading to an antitumor response which secondarily extends to muscle and skin, by cross‐reactivity and/or epitope spreading . Since anti‐TIF1γ IgG2 identified patients with poorer prognosis, the presence of anti‐TIF1γ IgG2 autoantibodies may reflect a helper T cell response associated with an inefficient antitumor response, which warrants further study.…”

“…Indeed, overexpression of TIF1γ is involved in the oncogenesis of breast cancer and in a significant proportion of colorectal adenocarcinomas . The parallel evolution of anti‐TIF1γ autoantibodies and cancer corroborates the potential role of tumors to promote an anti‐TIF1γ response that secondarily deviates towards muscle and skin . As with anti‐Hu–positive autoantibody in encephalitis or anti‐POL3–positive autoantibodies in systemic sclerosis , it is tempting to speculate that a tumor may harbor ectopically expressed or mutated TIF1γ antigens, leading to an antitumor response which secondarily extends to muscle and skin, by cross‐reactivity and/or epitope spreading .…”

Co-occurrence of Dermatomyositis and Polycythemia Unveiling Rare de Novo Neuroendocrine Prostate Tumor

“…Dermatomyositis seems to carry the highest relative risk compared to the general population, up to 5.5, followed by polymyositis with a relative risk 1.62 ( 2 ). Immune-mediated necrotizing myopathy, a recently described type of myositis, has also been linked to cancer, particularly in patients negative for antibodies against signal recognition particle (SRP) or positive against 3- hydroxy-3- methylglutaryl-coenzyme-A reductase (HMGCR) ( 3 ), although the latter are associated with statin-associated autoimmune myopathy as well ( 4 ). The risk of malignancy is usually highest the year preceding or following the myositis diagnosis and it seems to wane within 1–5 years post myositis diagnosis ( 1 ).…”

“…Our patient had dermatomyositis with several of those risk factors (male, older age, elevated inflammatory markers), although we did not test for anti-p155/TIF-1γ antibodies. A possible mechanism underlying the paraneoplastic manifestations could be the production of antibodies against tumor antigens cross-reacting with muscle antigens ( 3 , 6 ).…”

Cancer-associated Dermatomyositis: Does the PD-1 Checkpoint Pathway Play a Role?

“…It is well recognized that dermatomyositis (DM) is the inflammatory myopathy most often associated with cancer. In clinical practice, nearly one-third of patients with DM present with associated malignant disease, and the remainder may harbor an occult cancer that could develop in the near future, or never appear 1,2 . The immune system likely has a role in determining which of these outcomes will ensue.…”