Cancer-associated Myositis Research Articles

The Relationship Between Anti-Cell Division Cycle and Apoptosis Regulator 1 Autoantibodies, Anti-Sp4 Autoantibodies, and Cancer in Anti-Transcription Intermediary Factor 1γ-Positive Dermatomyositis.

The objective of this study was to describe the frequency, co-occurrence, and cancer association of anti-cell division cycle and apoptosis regulator 1 (anti-CCAR1) and anti-Sp4 in two large independent adult dermatomyositis (DM) cohorts. Anti-transcription intermediary factor 1γ (anti-TIF1γ)-positive patients with DM from two independent cohorts were studied to determine the serologic overlap of anti-CCAR1 and anti-Sp4 autoantibodies measured by enzyme-linked immunosorbent assay. Associations between cancer-associated myositis (CAM) and antibody-defined subgroups within anti-TIF1γ-positive patients with DM were determined. A total of 305 anti-TIF1γ-positive patients with DM were studied: 169 patients from Johns Hopkins and 136 patients from Stanford. In each cohort, approximately one-third of anti-TIF1γ-positive patients with DM were anti-Sp4 positive, one-third were anti-CCAR1 positive, 20% were positive for both, and half of patients were negative for both. There was a strong association with CAM in patients lacking both these antibodies (Johns Hopkins, odds ratio [OR] 12.9 [95% confidence interval (CI) 3.6-89.5]; Stanford, OR 4.5 [95% CI 1.8-13.2]). The strongest negative association with CAM was found in patients with anti-Sp4 or anti-CCAR1 (Johns Hopkins, OR 0.07 [95% CI 0.01-0.27]; Stanford, OR 0.22 [95% CI 0.07-0.55]). Both anti-Sp4 and anti-CCAR1 autoantibody subgroups are negatively associated with CAM. Although the magnitude of this association is substantial, cancer occasionally occurs in patients positive for either specificity. Conversely, approximately half of anti-TIF1γ-positive patients with DM are negative for both antibodies (anti-Sp4/anti-CCAR1 negative), and thus this subgroup may warrant more intensive cancer surveillance.

Cancer-associated myositis before and after the COVID-19 pandemic onset: a changing trend.

During the COVID-19 pandemic, there was a significant impact on the management of non-COVID-19 related diseases, potentially increasing the incidence of paraneoplastic syndromes such as cancer-associated myositis (CAM).The aim of this study is to determine the incidence of CAM in our cohort before and after the COVID-19 pandemic onset. We included patients with idiopathic inflammatory myopathy (IIM), diagnosed between June 2016 and June 2023. The patients were divided into two groups according to the date of IIM diagnosis. We included 132 patients; 65.1% (n=86) were diagnosed prior to and 34.9% (n=46) after the COVID-19 pandemic. The most common IIM was dermatomyositis (DM) before and after the COVID-19 pandemic onset (p=0.750). The most frequent myositis-specific antibody (MSA) before the COVID-19 pandemic was anti-Mi2 (15.1%). After the COVID-19 pandemic onset, anti-TIF1γ was the most common MSA (21.7%), with a significantly higher relative prevalence (p=0.006). The incidence of CAM was significantly higher after the COVID-19 pandemic onset (11 vs. 3 new cases, p<0.002). Patients with CAM more frequently had anti-TIF1γ-positivity (p<0.001) and a diagnosis after the pandemic (p=0.001) than non-CAM-IIM patients. No significant differences were found regarding vaccination status or previous COVID-19 infection in CAM and non-CAM-IIM patients. Diagnosis after the COVID-19 pandemic was an independent predictor of CAM among IIM patients (OR 0.012, 95% CI 0.000-0.400, p=0.013), regardless of age, sex or previous COVID-19 infection. There was a significant increase in the incidence of CAM after the COVID-19 pandemic. IIM diagnosis after the COVID-19 pandemic was an independent predictor of CAM.

Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies.

The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immunoassay (LIA) and particle-based multi-analyte technology (PMAT) in a multicenter cohort of patients with IIMs. We tested the sera from 411 patients affected with definite IIM, including 142 polymyositis (PM), 147 dermatomyositis (DM), 19 cancer-associated myositis, and 103 overlap myositis syndrome (OM), and from 269 controls. MSAs/MAAs were determined by 16Ags LIA in all sera, and anti-HMGCR by ELISA in 157/411 IIM sera and 91/269 control sera. The analytical specificity of LIA/HMGCR ELISA was compared with that of PMAT in 89 MSA+ IIM sera. MSAs/MAAs were positive in 307/411 (75%) IIM patients and 65/269 (24%) controls by LIA (Odds Ratio 9.26, 95% CI 6.43-13.13, p < 0.0001). The sensitivity/specificity of individual MSAs/MAAs were: 20%/100% (Jo-1), 3%/99.3% (PL-7), 4%/98.8% (PL-12), 1%/100% (EJ), 0.7%/100% (OJ), 9%/98% (SRP), 5.6%/99.6% (TIF1γ), 4.6%/99.6% (MDA5), 8%/96% (Mi-2), 1.5%/98% (NXP2), 1.7%/100% (SAE1), 4%/92% (Ku), 8.5%/99% (PM/Scl-100), 8%/96% (PM/Scl-75), and 25.5%/79% (Ro52). Anti-HMGCR was found in 8/157 (5%) IIM patients and 0/176 (0%) controls by ELISA (p = 0.007). Concordance between LIA/HMGCR ELISA and PMAT was found in 78/89 (88%) samples. Individual MSAs detected by LIA were associated with IIM subsets: Jo-1 with PM and OM, PL-12 with OM, Mi-2, TIF1γ, and MDA5 with DM, SRP with PM, and PM/Scl-75/100 with OM (p < 0.001 for all). Since MSAs are mostly mutually exclusive, multi-specific antibody profiling seems effective for a targeted clinical-serologic approach to the diagnosis of IIMs.

Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: results from the MYONET registry.

To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations and malignancy, between adults with anti-synthetase syndrome (ASyS) and DM. Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1γ/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V-sign, erythroderma, and/or periorbital rash). In total 1054 patients were included (DM, n = 405; ASyS, n = 649). In the ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease and cardiac involvement differentiated ASyS-DMskin from DM (all P < 0.001), whereas higher frequency of any of four DM-type rashes-heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V-sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%)-differentiated DM from ASyS-DMskin (all P < 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both P < 0.001). DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Cancer-Associated Myositis Associated with Esophageal Adenocarcinoma Detected on 18F-FDG Positron Emission Tomography/Computed Tomography: A Case Report and Review of Literature

Abstract A strong association between inflammatory myopathies and malignancy has been well-recognized. Cancer-associated myositis is thought to be a paraneoplastic syndrome due to the antitumor immunity secondary to similar tumor and regenerating muscle antigens. As the prognosis of myositis depends on the prognosis and treatment of the underlying malignancy, the treating doctor must determine the importance of detecting cancer-associated myositis and underlying cancer. 18 Fluorine-fluoro deoxy glucose/positron emission tomography/computed tomography is a sensitive tool that helps detect myositis in such patients. However, there are no clear guidelines regarding the best approach.

E079 Preliminary analysis of autoantibody profiles of autoimmune inflammatory myopathies: study from a single North Indian tertiary care centre

Abstract Background/Aims Studies in autoimmune inflammatory myositis (AIM) have shown a strong role of autoantibodies in the diagnosis and prognosis of patients with myositis. This ongoing study shares the preliminary data of 139 patients with AIM from a North Indian tertiary care centre. This prospective, observational study was conducted at a 1250-bedded hospital to assess the prevalence of myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) in patients from the Indian subcontinent with AIM and the correlation of these antibodies with clinical features. Methods From November 2016 to September 2022, patients with AIM (satisfying the Bohan and Peter criteria of 1975) attending the Rheumatology and Clinical Immunology Department of Medanta Hospital were included after taking their informed consent, and divided into subgroups as dermatomyositis (DM), polymyositis (PM), CTD-associated myositis (CTD-M), cancer-associated myositis (CAM), and juvenile myositis (JM). The Institutional Ethics Committee approved the study. Clinical data and sera from patients were collected and analysed. Results The study included 139 individuals with a mean age of 45.4 years. Fifty-two had DM, 49 had PM, 25 had CTD-M, 6 had CAM, and 7 had JM. ANA positivity was found in 67.70%, MSA in 22.3%, MAA in 25.4%, and both in 12.3%. Antibodies against Mi-2 were identified in 13 (28.9%) patients, Jo-1 in 14 (32.50%), PL-7 in 3 (6.7%), PL-12 in 4 (8.9%), SRP in 9 (20%), and MDA-5 and NXP2 in 1 (2.2%) patient each. Antibodies against Ro were found in 28 (57.1%) of the patients, RNP in 8 (16.3%), and PM-Scl in 9 (18.4%). Mi-2 antibodies were mostly identified in DM patients and were significantly associated with skin rash. SRP positivity was mostly found mainly in PM. Raynaud's and ILD were linked to the presence of Jo-1 and Ro antibodies. Malignancy screening was negative in NXP2 and TIF1γ antibody-positive patients. Conclusion MSA was found in 22.3% of cases and MAA in 25.4%. Mi-2 antibodies were linked to rash, but none had ILD, whereas Jo-1 antibodies were linked to mechanic hands, arthritis, and ILD. We aim to gather more strong results in the future as additional patients are recruited in this continuing trial. Disclosure S. Dhuria: None. P. Khatri: None. N. Negalur: None. K. Telang: None. S. Ghosh: None. D. Yadavalli: None. V. Singal: None. R. Gupta: None.

P148 Long-term survival of patients with idiopathic inflammatory myopathies: Anatomy of a single-center cohort

Abstract Background/Aims Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of immune-mediated systemic diseases, characterized by muscle inflammation and multiple systemic manifestations. We aimed to characterize clinical manifestations, course, treatment, and mortality of IIM patients. We have also attempted to assess predictors of mortality in IIM. Methods Retrospective single center study IIM patients followed between 1980 and June 2022, including IIM patients fulfilling three or four of the Bohan and Peter criteria. Patients were divided in 6 groups: adult-onset polymyositis (APM), adult-onset dermatomyositis (ADM), juvenile-onset dermatomyositis (JDM), ‘overlap’ myositis (OM), cancer-associated myositis (CAM), and antisynthetase syndrome (ASyS). Sociodemographic, clinical and immunological features and treatment were collected. Additionally, disease complications and causes of death were recorded. The log rank test was used to compare survival curves between subgroups. The Cox proportional hazards regression was used to assess predictors of mortality. Results A total of 158 patients were included with a mean age at diagnosis of 40.81±15.63 years. Most patients were female (77.2%) and Caucasian (63.9%). The most frequent diagnoses were ADM (35.4%), OM (20.9%) and APM (24.7%), respectively. The majority of patients presented with both upper and lower limb involvement (89.2%), with a mean creatinine kinase level of 4423 ± 7633 U/L. Electromyography, muscle biopsy and magnetic resonance were positive for active myositis in 81.3% (104/128), 77.7% (101/130) and 40.9% (54/132), respectively. Antinuclear antibodies were positive in 62.4% of the patients. Remitting and relapsing (RR) was the most common disease course (35.4%). Most patients were treated with a combination of steroids and one-to-three immunosuppressive drugs (74.1%). Interstitial lung disease, gastrointestinal and cardiac involvement were frequent, affecting 38.5%, 36.5% and 23.4% of the patients, respectively. The survival rates at 5, 10, 15, 20 and 25 years of follow-up were 89%, 74%, 67%, 62% and 43%, respectively. During a median follow up of 13.61 ± 10.24 years, 46 (29.1%) have died, mainly due to infection (28.3%), followed by malignancy (19.6%) and cardiovascular events (10.9%). Positive biopsy (p = 0.044), Jo-1 (p = 0.039), malignancy (p = 0.026), cardiac involvement (p = 0.011) and infections (p = 0.016) were associated with mortality. Older age at diagnosis (HR:1.058, 95CI 1.031-1.085), cardiac involvement (HR: 3.23, 95CI 1.60-6.53), and malignancy (HR 2.20, 95CI 1.09-4.44) were independent predictors of mortality. Conclusion IIM is a rare disease with important systemic complications. Older age at diagnosis, cardiac involvement, and malignancy are independent predictors on mortality. Early diagnosis and aggressive treatment of cardiac involvement could improve survival of these patients. Disclosure F. Guimarães: None. R. Yildirim: None. D.A. Isenberg: None.

Long-term survival of patients with idiopathic inflammatory myopathies: anatomy of a single-centre cohort.

We aimed to characterise clinical manifestations, disease course, treatment, and mortality of IIM patients. We have also attempted to identify predictors of mortality in IIM. This was a retrospective single-centre study including IIM patients fulfilling the Bohan and Peter criteria. Patients were divided in 6 groups: adult-onset polymyositis (APM), adult-onset dermatomyositis (ADM), juvenile-onset dermatomyositis, 'overlap' myositis (OM), cancer-associated myositis, and antisynthetase syndrome. Sociodemographic, clinical and immunological features, treatment, and causes of death were recorded. Survival analysis and predictors of mortality was performed using Kaplan-Meier and Cox proportional hazards regression. A total of 158 patients were included with a mean age at diagnosis of 40.8±15.6 years. Most patients were female (77.2%) and Caucasian (63.9%). The most frequent diagnoses were ADM (35.4%), OM (20.9%) and APM (24.7%), respectively. Most patients (74.1%) were treated with a combination of steroids and one-to-three immunosuppressive drugs. Interstitial lung disease, gastrointestinal and cardiac involvement affected 38.5%, 36.5% and 23.4% of the patients, respectively. The survival rates at 5, 10, 15, 20 and 25 years of follow-up were 89%, 74%, 67%, 62% and 43%, respectively. During a median follow-up of 13.6±10.2 years, 29.1% have died, infection being the most common cause (28.3%). Older age at diagnosis (HR1.053, 95% CI 1.027-1.080), cardiac involvement (HR 2.381, 95% CI 1.237-4.584), and infections (HR 2.360, 95% CI 1.194-4.661) were independent predictors of mortality. IIM is a rare disease with important systemic complications. Early diagnosis and aggressive treatment of cardiac involvement and infections could improve survival of these patients.

Paraneoplastic syndromes in rheumatology

Paraneoplastic syndromes in rheumatology are agroup of canonical rare rheumatic diseases with musculoskeletal involvement that occur in close temporal and causal association with malignancies. Knowledge of these possibly enables aprognostically relevant early diagnosis of the underlying malignant disease. In the era of immune checkpoint inhibitor treatment, there are first indications of an increase in the incidence and severity of paraneoplastic syndromes, so that they are becoming of increasing importance for the practicing rheumatologist. These nine syndromes, paraneoplastic arthritis, palmar fasciitis and polyarthritis, remitting seronegative symmetrical synovitis with pitting edema, pancreatic panniculitis with polyarthritis, paraneoplastic vasculitis, cancer-associated myositis, hypertrophic osteoarthropathy (Marie-Bamberger), eosinophilic fasciitis and tumor-induced osteomalacia, usually occur with characteristic courses and sometimes pathognomonic clinical manifestations, which are presented in this article accompanied by the rational use of a diagnostic algorithm for tumor detection. With frequently disappointing therapeutic response to glucocorticoids, nonsteroidal antirheumatic drugs and immunosuppressants, treatment of the underlying malignant disease represents the crucial step in the treatment of paraneoplastic syndromes.

Tertiary lymphoid structures in the primary tumor site of patients with cancer-associated myositis: A case-control study.

To investigate histologic features of immunological components in the primary tumor site of patients with cancer-associated myositis (CAM) by focusing on tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs), which play major roles in antitumor immunity. Cancer-associated myositis patients were selected from the single-center idiopathic inflammatory myopathy cohort based on the availability of primary tumor specimens obtained before the introduction of immunomodulatory agents. Control cancer subjects without CAM were selected from the cancer tissue repository at a ratio of 1:2 matched for demographics and cancer characteristics of CAM cases. A series of immunohistochemical analyses was conducted using sequential tumor sections. TLS was defined as an ectopic lymphoid-like structure composed of DC-LAMP+ mature dendritic cells, CD23+ follicular dendritic cells (FDCs) and PNAd+ high endothelial venules. TLS distribution was classified into the tumor center, invasive margin, and peritumoral area. Six CAM patients and 12 matched non-CAM controls were eligible for the study. There was no apparent difference in the density or distribution of TILs between the groups. TLSs were found in 3 CAM patients (50%) and 4 non-CAM controls (33%). TLSs were exclusively located at the tumor center or invasive margin in CAM cases but were mainly found in the peritumoral area in non-CAM controls. FDCs and class-switched B cells colocalized with follicular helper T cells were abundantly found in the germinal center-like area of TLSs from CAM patients compared with those from non-CAM controls. The adaptive immune response within TLSs in the primary tumor site might contribute to the pathogenic process of CAM.

Cancer associated autoantibodies in idiopathic inflammatory myopathies: A retrospective cohort from a single center in China

ObjectivesIdiopathic inflammatory myopathies (IIMs) are systemic, heterogeneous diseases, which mainly affect skeletal muscle. Myositis with cancer is often referred to as cancer-associated myositis (CAM), which is associated with poor prognosis. This study aimed to determine the cancer associated myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with IIMs. MethodsThis retrospective study enrolled 312 patients with IIMs who were treated at Tianjin Medical University General Hospital, China, from January 2015 to December 2020. Clinical data were collected. Serum MSAs, including anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ and anti-HMGCR antibodies were detected. Cancer-associated MSAs, their phenotypic and survival features were estimated through SPSS 20.0. ResultsThe results revealed that anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies with odds ratios (95% CI) of 8.70 (3.35–22.64) and 22.31 (4.32–115.05), respectively. Skin lesions, proximal weakness, dysphagia and dysarthria were observed more frequently in patients carrying anti-TIF1-γ antibody. By contrast, patients with anti-TIF1-γ antibody had a lower frequencies of fever, arthritis/arthralgia and interstitial lung disease (ILD). Anti-TIF1-γ antibody positive CAM comprised about half of CAM entities and had the characteristic of close temporal association with cancer detection/recurrence. Female-dominant, common reproductive system tumors were other clinical features of this subset. Besides, patients with anti-TIF1-γ antibody positive had significantly lower survival rates than the anti-TIF1-γ antibody negative group. ConclusionsAnti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies. Anti-TIF1-γ antibody positive CAM was a subset that comprised about half of CAM entities and had the characteristic of poor prognosis.

Genetic Influences in Cancer-Associated Myositis.

Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.

Management of Cancer-Associated Myositis.

Purpose of the ReviewCancer-associated myositis (CAM) is defined as when cancer appears within 3 years of myositis onset. Dermatomyositis and seronegative immune–mediated necrotizing myopathy are the phenotypes mostly related to cancer. In general, treatment principles in myositis patients with and without CAM are similar. However, some aspects of myositis management are particular to CAM, including (a) the need for a multidisciplinary approach and a close relationship with the oncologist, (b) the presence of immunosuppressive and antineoplastic drug interactions, and (c) the role of the long-term immunosuppressive therapy as a risk factor for cancer relapse or development of a second neoplasm. In this review, we will also discuss immunotherapy in patients treated with checkpoint inhibitors as a treatment for their cancer.Recent FindingsStudies on cancer risk in patients treated with long-term immunosuppressive drugs, in autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis, and in solid organ transplant recipients have shed some light on this topic. Immunotherapy, which has been a great advance for the treatment of some types of malignancy, may be also of interest in CAM, given the special relationship between both disorders.SummaryManagement of CAM is a challenge. In this complex scenario, therapeutic decisions must consider both diseases simultaneously.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40674-022-00197-2.

Update on dermatomyositis.

This review summarizes and comments on current knowledge in dermatomyositis. The 2018 European Neuromuscular Centre classification of dermatomyositis has been challenging by the discovery of clinicopathological features associated with dermatomyositis-specific antibody (DMSA) that were not incorporated in the original criteria. These features include but may not be limited to the presence of perifascicular necrosis in anti-Mi-2 dermatomyositis; presence of diffuse nonperifascicular sarcoplasmic myxovirus resistance protein A expression in anti-MDA5 dermatomyositis; and dermatomyositis sine dermatitis in anti-NXP-2 dermatomyositis. Variations and subclassifications within the same DMSA subtypes are observed: anti-MDA5 dermatomyositis is clinically subcategorized into good, intermediate, and poor prognostic subgroups; concurrent anti-CCAR1 and anti-TIF1-γ positivity identify anti-TIF1-γ-positive patient with a lower risk for cancer-associated myositis. Owing to distinct IFN1-signaling pathway activation in dermatomyositis, JAK-STAT inhibitor - the pathway-targeted therapy, have been studied with promising results in refractory dermatomyositis and some new-onset dermatomyositis. In addition, the potential serum biomarkers for IFN1 pathway activation are being investigated for their performance in monitoring the disease activity and the efficacy of the treatment. DMSA, evidence of prominent IFN1 pathway activation, and risk/severity-associated biomarkers would likely play major roles in future dermatomyositis classification, disease monitoring, and treatment decision.

Cancer associated autoantibodies in idiopathic inflammatory myopathies: A retrospective cohort from a single center in China

ObjectivesIdiopathic inflammatory myopathies (IIMs) are systemic, heterogeneous diseases, which mainly affect skeletal muscle. Myositis with cancer is often referred to as cancer-associated myositis (CAM), which is associated with poor prognosis. This study aimed to determine the cancer associated myositis-specific autoantibodies (MSAs) and to elucidate their associations with clinical features in Chinese patients with IIMs. MethodsThis retrospective study enrolled 312 patients with IIMs who were treated at Tianjin Medical University General Hospital, China, from January 2015 to December 2020. Clinical data were collected. Serum MSAs, including anti-Mi-2, anti-TIF1-γ, anti-NXP2, anti-SAE, anti-MDA5, anti-SRP, anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ and anti-HMGCR antibodies were detected. Cancer-associated MSAs, their phenotypic and survival features were estimated through SPSS 20.0. ResultsThe results revealed that anti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies with odds ratios (95% CI) of 8.70 (3.35–22.64) and 22.31 (4.32–115.05), respectively. Skin lesions, proximal weakness, dysphagia and dysarthria were observed more frequently in patients carrying anti-TIF1-γ antibody. By contrast, patients with anti-TIF1-γ antibody had a lower frequencies of fever, arthritis/arthralgia and interstitial lung disease (ILD). Anti-TIF1-γ antibody positive CAM comprised about half of CAM entities and had the characteristic of close temporal association with cancer detection/recurrence. Female-dominant, common reproductive system tumors were other clinical features of this subset. Besides, patients with anti-TIF1-γ antibody positive had significantly lower survival rates than the anti-TIF1-γ antibody negative group. ConclusionsAnti-TIF1-γ antibody and anti-SAE antibody were cancer-associated autoantibodies. Anti-TIF1-γ antibody positive CAM was a subset that comprised about half of CAM entities and had the characteristic of poor prognosis.

Risk of cancers in polymyositis and dermatomyositis

Idiopathic inflammatory myopathy (IIM) is a rare autoimmune disease that women are more often diagnosed. The most common IIM are polymyositis (PM) and dermatomyositis (DM). More often than in other rheumatic diseases, various neoplasms develop in their course (CAM, cancer-associated myositis). The most common cancers included ovarian and reproductive organs cancer, breast, lung, gastrointestinal and hematopoietic cancer (mainly non-Hodgkin’s lymphomas), melanoma, and nasopharyngeal cancer (the last one is widespread in Southeast Asia). It is worth emphasizing that a neoplastic disease may develop in IIM, and IIM may be a factor influencing the initiation of carcinogenic processes. The presented manuscript discusses the symptoms occurring in their course CAM and the risk factors for cancer development in detail. The importance of clinical observation of patients with PM/DM and the necessity of quick oncological diagnostics in the case of suspicion of such a process was discussed and emphasized (including the importance of screening tests).

The Genetics of Autoimmune Myositis.

The idiopathic inflammatory myopathies (IIM) are rare, heterogeneous systemic autoimmune disorders, characterized by inflammation of skeletal muscle and multi-organ involvement. Studies to identify genetic risk factors and dysregulated gene expression in IIM aim to increase our understanding of disease pathogenesis. Genome-wide association studies have confirmed the HLA region as the most strongly associated region in IIM, with different associations between clinically-defined subgroups. Associated genes are involved in both the innate and adaptive immune response, while identification of variants reported in other autoimmune disorders suggests shared biological pathways. Targeted imputation analysis has identified key associated amino acid residues within HLA molecules that may influence antigen recognition. These amino acids increase risk for specific clinical phenotypes and autoantibody subgroups, and suggest that serology-defined subgroups may be more homogeneous. Recent data support the contribution of rare genetic variation to disease susceptibility in IIM, including mitochondrial DNA variation in sporadic inclusion body myositis and somatic mutations and loss of heterozygosity in cancer-associated myositis. Gene expression studies in skeletal muscle, blood and skin from individuals with IIM has confirmed the role of interferon signalling and other dysregulated pathways, and identified cell-type specific signatures. These dysregulated genes differentiate IIM subgroups and identify potential biomarkers. Here, we review recent genetic studies in IIM, and how these inform our understanding of disease pathogenesis and provide mechanistic insights into biological pathways.

Development of dermatomyositis after anti-transcriptional intermediary factor 1-γ antibody seroconversion during treatment for small cell lung cancer

BackgroundInflammatory myositis, such as dermatomyositis, is sometimes complicated by cancer and is recognized as cancer-associated myositis. Although some autoimmune antibodies are considered to be involved in the development of myositis in cancer patients, the precise mechanism has not been clarified. The findings of the present case shed light on the mechanism by which anti-transcriptional intermediary factor 1 (TIF1)-γ Ab was produced and the pathogenesis of cancer-associated myositis.Case presentationWe describe a case of dermatomyositis that developed in a 67-year-old man who had been diagnosed with small cell lung cancer of clinical T4N3M0 stage IIIB/limited disease during treatment. He received systemic chemotherapy and radiation therapy, and dermatomyositis developed along with a significant decrease in tumor size. TIF1-γ Ab, which is one of the myositis-specific antibodies, was found to be seroconverted. In addition, immunohistochemical analysis showed that cancer cells were positive for the TIF1-γ antigen.ConclusionThe findings of the present case suggest that transcriptional intermediary factor 1-γ, which is released from tumor cells, induces the production of TIF1-γ Ab, leading to the development of dermatomyositis.

Serum levels of anti-transcriptional intermediary factor 1-γ autoantibody associated with the clinical, pathological characteristics and outcomes of patients with dermatomyositis

ObjectiveTo investigate the association of the serum levels of anti-transcriptional intermediary factor 1 (TIF1)-γ autoantibodies with the clinical and pathological characteristics, as well as the prognosis of adult patients with dermatomyositis (DM). MethodsEighty-seven adult DM patients with anti-TIF1-γ autoantibodies positive screened by immunoblotting assay were enrolled in the study. The presence and levels of anti-TIF1-γ autoantibodies were examined through enzyme-linked immunosorbent assay (ELISA). Muscle biopsy specimens were obtained from 52 patients, and immunohistochemistry was performed to visualize major histocompatibility complex (MHC)-I, CD3, CD20 and C5b-9. Muscle biopsy scores and disease activity were evaluated. ResultsA total of 80 patients were positive for anti-TIF1-γ autoantibodies confirmed by ELISA assay, including 30 cancer-associated myositis (CAM) and 50 non-CAM. Serum levels of anti-TIF1-γ autoantibodies did not significantly differ between the CAM and non-CAM groups. The levels of anti-TIF1-γ were associated with disease activity scores. A total of 63.9% of non-CAM patients displayed a classical DM pathological phenotype. Conversely, CAM patients presented with classical DM (25%), immune-mediated necrotizing myopathy (25%), non-specific myositis (32.3%), and normal (18%) phenotypes of muscle biopsy. Anti-TIF1-γ autoantibody levels were positively associated with muscle biopsy total scores, muscle fiber scores and inflammatory infiltration scores in the non-CAM patients but not in the CAM patients. The survival rate of CAM patients presenting with high anti-TIF1-γ autoantibody levels was lower than that of patients with low levels. However, no difference in survival rate was observed in the non-CAM group between high and low autoantibody levels. ConclusionThe distinct associations of anti-TIF1-γ autoantibody levels with disease activity, muscle histopathology damage and outcome indicated that different pathogenesis might be involved in DM with or without cancer.

Clinical value of cancer-associated myositis-specific antibodies, anti-transcriptional intermediary factor 1-γ, and anti-nuclear matrix protein 2 antibodies in a retrospective cohort of dermatomyositis/polymyositis in a Japanese community hospital.

Among the myositis-specific antibodies (MSA), anti-transcriptional intermediary factor 1 (TIF1)-γ and anti-nuclear matrix protein 2 (NXP2) antibodies are reportedly associated with cancer-associated myositis (CAM). We aimed to investigate patient characteristics of CAM and the clinical role of cancer-associated MSA (caMSA) in a retrospective cohort from a city hospital. All patients visiting our department between April 2014 and October 2021 with newly diagnosed dermatomyositis, polymyositis, and clinically amyopathic dermatomyositis were included. Anti-TIF1-γ and anti-NXP2 antibodies were collectively considered as caMSA. First, we compared clinical characteristics in CAM, defined as cases showing onset or recurrence of malignancy within 5years, versus non-CAM. Second, we investigated independent risk factors for CAM. Third, we compared clinical characteristics with and without caMSA within CAM. Finally, we investigated whether caMSA was predictive of poor prognosis. The cohort of 39 patients included 12 (30.7%) CAM cases. Compared with non-CAM, CAM had significantly more dermatomyositis and higher frequencies of dysphagia, anti-TIF1-γ antibody, and caMSA. Using logistic regression analysis, caMSA was an independent risk factor for CAM. In a comparison between caMSA and non-caMSA within CAM, caMSA was associated with higher frequencies of stage ≥ II. However, caMSA did not necessarily indicate a poor prognosis. Only caMSA represented an independent risk factor for CAM and showed a significant association with advanced cancer. Key Points • Cancer-associated MSA was an independent risk factor for cancer-associated myositis. • Cancer-associated MSA was associated with advanced cancer.