Abstract
BackgroundCancer is a significant complication contributing to increased mortality in idiopathic inflammatory myopathies (IIMs), and the association between IIMs and cancer has been extensively reported. Myositis-specific autoantibodies (MSAs) can help to stratify patients into more homogeneous groups and may be used as a biomarker for cancer-associated myositis. In this study, we aimed to systematically define the cancer-associated MSAs in IIMs.MethodsSerum from 627 patients with IIMs was tested for MSAs. The cancer risk with different MSAs was estimated by standardized incidence ratio (SIR). Paraneoplastic manifestation, such as the close temporal relationship between myositis onset and cancer diagnoses in patients with different MSAs, was also evaluated.ResultsCompared with the general Chinese population, patients with IIMs and anti-transcriptional intermediary factor (TIF1)-γ antibodies (SIR = 17.28, 95% CI 11.94 to 24.14), anti-nuclear matrix protein (NXP2) antibodies (SIR = 8.14, 95% CI 1.63 to 23.86), or anti-SAE1 antibodies (SIR = 12.92, 95% CI 3.23 to 32.94), or who were MSAs-negative (SIR = 3.99, 95% CI 1.96 to 7.14) faced increased risk of cancer. There was no association between specific MSAs subtypes and certain types of cancer. Paraneoplastic manifestations were observed in the patients carrying anti-TIF1-γ, as well as other MSAs. There were no prognostic differences among the patients with cancer-associated myositis (CAM) from different MSAs subgroups. However, in comparison to those with cancer unrelated to myositis, CAM had a worse prognosis, with an age-adjusted and sex-adjusted Cox hazard ratio (HR) of 10.8 (95% CI 1.38-84.5, p = 0.02) for all-cause mortality.ConclusionsOur study demonstrates in what is, to our knowledge, the largest population examined to date, that anti-SAE1, and previously reported anti-TIF1-γ and anti-NXP2 antibodies, are all associated with an increased risk of cancer in patients with IIMs. Moreover, our data suggest that in some cases, anti-HMGCR, anti-Jo-1 and anti-PL-12 antibody production might also be driven by malignancy. This can aid in the etiologic research of paraneoplastic myositis and clinical management.
Highlights
Cancer is a significant complication contributing to increased mortality in idiopathic inflammatory myopathies (IIMs), and the association between IIMs and cancer has been extensively reported
Besides anti-TIF1-γ antibodies, a few studies have indicated that the presence of other Myositis-specific autoantibodies (MSAs), including anti-nuclear matrix protein (NXP2), anti-Jo-1, anti-Mi-2β, anti-HMGCR, is correlated with cancer in IIMs as well [3,4,5,6,7,8,9,10,11,12], but these findings have not been consistently replicated in other studies [13,14,15,16]
Among these individuals who collectively had malignancies, 38 tested positive for anti-TIF1-γ, 3 for anti-NXP2, 4 for anti-SAE1, 10 for anti-aminoacyl-tRNA-synthetase antibodies, 1 each for anti-MDA5, anti-HMGCR, and anti-SRP, and 14 patients were MSAs- negative
Summary
Cancer is a significant complication contributing to increased mortality in idiopathic inflammatory myopathies (IIMs), and the association between IIMs and cancer has been extensively reported. We aimed to systematically define the cancer-associated MSAs in IIMs. Idiopathic inflammatory myopathies (IIMs) are a group of acquired, heterogeneous, systemic diseases that mainly affect skeletal muscle, of which polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis (sIBM) are the main clinical subtypes [1]. The conflicting findings on the association between increased cancer risk and IIM subtypes may possibly be due to the significant clinical heterogeneity of patients with IIMs. Interestingly, myositis-specific autoantibodies (MSAs) are found exclusively in IIMs and can help to stratify patients into more homogeneous groups [2]. Myositis-specific autoantibodies (MSAs) are found exclusively in IIMs and can help to stratify patients into more homogeneous groups [2] It is well-known that adult patients with dermatomyositis (DM) who carry anti-transcriptional intermediary factor (TIF1)-γ are more likely to develop malignancy than anti-TIF1-negative patients. Besides anti-TIF1-γ antibodies, a few studies have indicated that the presence of other MSAs, including anti-nuclear matrix protein (NXP2), anti-Jo-1, anti-Mi-2β, anti-HMGCR, is correlated with cancer in IIMs as well [3,4,5,6,7,8,9,10,11,12], but these findings have not been consistently replicated in other studies [13,14,15,16]
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