They were also found at a similar frequency in patients with other inflammatory myopathies, SLE, SSc, and rheumatoid arthritis, but rarely (1%) in healthy controls. disease-specific autoantigens that are closely tied with risk of cancer emergence. The best-described examples of this are antibodies against anti-RNA polymerase III (anti-POL3) and transcription intermediary factor 1-gamma (anti-TIF1). Patients with systemic sclerosis and cancer that are diagnosed within a short time interval of each other frequently have anti-POL3 antibodies. Similarly, in the dermatomyositis spectrum, the majority of anti-TIF1-associated cancers are detected around the time of DM onset (most often within 1 year). Antibodies against the minor spliceosome complex containing RNA Binding Region Containing 3 (RNPC3) are also associated with increased cancer incidence in SSc. For DM, antibodies against Nuclear Matrix Protein 2 (NXP2) are also RAB5A potentially associated with increased cancer emergence. The systemic sclerosis/anti-POL3 connection with close cancer onset led to the 2C-C HCl first experiments directly supporting the concept that rheumatic disease may in fact be a manifestation of cancer. It is now clear that studying these diseases through the lens of autoantibodies can reveal relationships and insights that would otherwise remain obscured. Extending these studies, new findings show that antibodies against RNA polymerase I large subunit are associated with protection against short interval cancers in anti-POL3-positive systemic sclerosis patients. These insights highlight the fact that autoantigen discovery related to cancer emergence remains an important priority; such new tools will enable the testing of specific hypotheses regarding mechanisms governing disease emergence and development of effective anti-tumor responses. Autoantibody phenotype will likely play an important role in the development of cancer screening guidelines that are critically needed by clinicians taking care of these patients. In this review we will summarize the current state of knowledge regarding the different ways in which autoantibodies are connected with systemic sclerosis/dermatomyositis and malignancy and highlight potential paths forward. Keywords:Autoimmunity, cancer, systemic sclerosis, scleroderma, dermatomyositis, autoantibody == Introduction == It has long been recognized that patients with autoimmune rheumatic diseases are at higher risk of cancer than the general population; this is especially true for those with systemic sclerosis (SSc) and dermatomyositis (DM). Why this should be so has been elusive, and there are many potential explanations (not necessarily mutually exclusive). These include the possibility of a common genetic predisposition, or inciting exposure (eg, some environmental influence) that may confer susceptibility to both diseases. Also possible is that tissue damage caused by the autoimmune disease itself may lead to an increased risk of cancer, as may the cytotoxic therapies used to treat these diseases. An elegant study performed on patients with scleroderma and cancer provided compelling 2C-C HCl evidence that in some cases, autoimmunity may be initiated by autoantigen mutation in the patients cancer [1]. That the majority of patients with the same form of 2C-C HCl SSc 2C-C HCl and autoantibody response do not manifest a cancer remained an unexplained but important biologic clue. Recent findings following up on this thread now suggest that broader immune (anti-tumor) responses more successfully eliminate any underlying cancers (discussed below). This has put a new focus on the previously under-appreciated role of autoantibodies as unique tools to explore and understand this interface. In this review, we will focus on SSc and DM and specific autoantibodies to illustrate how they provide a unique opportunity to interrogate the interface of autoimmunity and cancer. New information from these studies will afford important insights into the mechanisms underlying the autoimmune rheumatic diseases, and will enable tools to be developed that can more precisely predict and stratify cancer risk amongst these patient populations. Ultimately, studies at the cancer autoimmunity interface will likely be of broader utility in the general population as this new information will illuminate the natural immune response to human cancers. == Systemic Sclerosis and.