Anti-transcriptional Intermediary Factor Research Articles

Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America.

Myositis-specific autoantibodies have defined distinct phenotypes of patients with juvenile myositis (JIIM). We assessed the frequency and clinical significance of anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody-associated JIIM in a North American registry. Retrospective examination of the characteristics of 35 JIIM patients with anti-MDA5 autoantibodies was performed, and differences from other myositis-specific autoantibody groups were evaluated. Anti-MDA5 autoantibodies were present in 35/453 (7.7%) of JIIM patients and associated with older age at diagnosis, and lower serum creatine kinase and aldolase levels. Patients with anti-MDA5 autoantibodies had more frequent weight loss, adenopathy, arthritis, interstitial lung disease (ILD), and less frequent falling compared with anti-transcriptional intermediary factor 1 (TIF1), anti-nuclear matrix protein 2 (NXP2)and myositis-specific autoantibody/myositis-associated autoantibody-negative patients. They had a different season of diagnosis and less frequent mechanic's hands and ILD compared with those with anti-synthetase autoantibodies. Anti-MDA5 patients received fewer medications compared with anti-TIF1, and corticosteroid treatment was shorter compared with anti-TIF1 and anti-nuclear matrix protein 2 autoantibody groups. The frequency of remission was higher in anti-MDA5 than anti-synthetase autoantibody-positive JIIM. In multivariable analyses, weight loss, arthritis and arthralgia were most strongly associated with anti-MDA5 autoantibody-positive JIIM. Anti-MDA5 JIIM is a distinct subset, with frequent arthritis, weight loss, adenopathy and less severe myositis, and is also associated with ILD. Anti-MDA5 is distinguished from anti-synthetase autoantibody-positive JIIM by less frequent ILD, lower creatine kinase levels and differing seasons of diagnosis. Anti-MDA5 has comparable outcomes, but with the ability to discontinue steroids more rapidly and less frequent flares compared with anti-TIF1 autoantibodies, and more frequent remission compared with anti-synthetase JIIM patients.

Myositis-specific autoantibodies and their clinical associations in idiopathic inflammatory myopathies.

Myositis-specific autoantibodies (MSAs) have been found to be present predominantly in patients with idiopathic inflammatory myopathies (IIMs). This study aimed to investigate the prevalence of MSAs and their associated complications in a cohort of patients with IIMs. This was a multicentered prospective study. Consecutive adult Chinese patients with IIMs in the regional hospitals in Hong Kong were followed up from July 2016 to January 2018. Clinical characteristics, treatment history, and disease complications were documented. A commercially available immunoblot assay was used to detect the MSAs. Out of the 201 patients studied, at least one MSA was found in 63.2% of patients. The most common among the identified MSAs were the anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) and the anti-transcriptional intermediary factor 1-gamma antibody (anti-TIF1-γ Ab) (both 13.9%), followed by anti-Jo-1 antibody (12.4%). Anti-MDA5 was present exclusively in dermatomyositis (DM) and was strongly associated with digital ulcers, amyopathy, and rapidly progressive interstitial lung disease (RP-ILD). Anti-TIF1γ was strongly associated with refractory rash and malignancy. Independent risk factors of RP-ILD included anti-MDA5 (OR 14.5), clinically amyopathic DM (OR 13.9), and history of pulmonary tuberculosis (OR 12.2). Cox regression analysis showed that anti-TIF1γ (HR 3.55), DM (HR 3.82), and family history of cancer (HR 3.40) were independent predictors of malignancy. MSA testing enables dividing of patients with IIMs into phenotypically homogeneous subgroups and prediction of potentially life-threatening complications.

Clinical features of anti-transcription intermediary factor 1γ (TIF1γ)-positive dermatomyositis with internal malignancy and investigation of the involvement of TIF1γ expression in tumors in the pathogenesis of cancer-associated dermatomyositis.

Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibody (Ab) is significantly associated with internal malignancies in adult patients with dermatomyositis (DM). Although pathogenesis of cancer-associated DM is unknown, TIF1γ overexpression in tumors has been considered to be critical for the development of DM. The objective of this study was to investigate clinical characteristics of patients with anti-TIF1γ Ab-positive DM and elucidate risk factors that are potentially associated with internal malignancy. In addition, we compared the expression of TIF1γ in tumor tissues of patients with anti-TIF1γ Ab-positive DM, anti-TIF1γ Ab-negative DM and without DM in order to investigate the pathogenesis of cancer-associated DM. We analyzed 77 Japanese patients with DM, and found 19 patients to be positive for anti-TIF1γ Ab. Patients with anti-TIF1γ Ab-positive DM were older and presented heliotrope rash and flagellate erythema more frequently than patients without anti-TIF1γ Ab (P<0.05). Interstitial lung disease (ILD) and rapidly progressive ILD, as well as palmar violaceous erythema, were less frequent in patients with anti-TIF1γ Ab than in patients without. Furthermore, internal malignancy and dysphagia were significantly more frequent in the anti-TIF1γ Ab-positive group (P<0.01). Male sex and dysphagia were significantly associated with internal malignancy in patients with anti-TIF1γ Ab-positive DM (P<0.01 and <0.05, respectively). Using immunohistochemistry, we examined the TIF1γ expression in tumors of 11 patients with cancer-associated DM (anti-TIF1γ Ab-positive, nine; anti-TIF1γ Ab-negative, two) and 25 patients without DM. TIF1γ was highly expressed in all tumors, and there was no significant difference in TIF1γ expression between patients with and without DM. Furthermore, TIF1γ expressions in tumors were similar irrespective of the presence of anti-TIF1γ Ab. These results suggest that anti-TIF1γ antibody may not be simply induced by overexpression of TIF1γ in tumors in patients with DM, but that other mechanisms may exist.

Rhabdomyolysis and COVID-19 Infection: Is It Due to Statin Use or Anti-TIF1-y Antibodies?

Coronavirus disease 2019 (COVID-19), now a global pandemic, has infected millions of people and caused hundreds of thousands of deaths. Neurological presentation of the novel coronavirus includes headaches, seizures, myalgias, hyposmia, ageusia, etc. Guillain-Barre Syndrome (GBS) and its variant, Miller Fisher Syndrome, have been reported in COVID-19 patients presenting with lower limb weakness, paresthesia, facial diplegia, and ataxia. Most recently, large vessel occlusion strokes were seen in infected younger patients without vascular risk factors. We present a novel case of rhabdomyolysis associated with COVID-19 infection in a patient on atorvastatin, in whom we detected positive anti-transcriptional intermediary factor 1 gamma antibodies (anti-TIF1-y Ab). Bilateral upper and lower extremity weakness improved with aggressive fluid administration and intravenous immunoglobulin (IVIg) at 0.4mg/kg for a total of 5 days. Interrupting a strong cytokine response with IVIg early on during the disease may have led to rapid improvement.

A single-center, retrospective record review of malignancy prevalence in patients with dermatomyositis with anti-transcription intermediary factor 1γ antibodies via line immunoassay versus immunoprecipitation

To the Editor: The association of dermatomyositis (DM) with malignancy has been well established, with a prevalence between 11% and 42%.1 Patients with DM with transcription intermediary factor 1γ (TIF-1γ) antibodies appear to be at greater risk of malignancy than the broader population of patients with DM, with a malignancy prevalence between 42% and 100%.2

Clinically amyopathic dermatomyositis with anti-transcriptional intermediary factor 1-γ autoantibody positivity.

Clinically amyopathic dermatomyositis with anti-transcriptional intermediary factor 1-γ autoantibody positivity.

Clinical significance of serum levels of anti-transcriptional intermediary factor 1-γ antibody in patients with dermatomyositis.

Dermatomyositis (DM) is an autoimmune inflammatory disease characterized by skin eruptions and myositis. Anti-transcriptional intermediary factor 1-γ antibody (anti-TIF1-γ Ab) is one of the most frequently detected myositis-specific autoantibodiesand adults positive for anti-TIF1-γ have markedly higher rates of malignancy. Our aim was to determine the clinical associations of anti-TIF1-γ levels in 31 Japanese adult DM patients positive for anti-TIF1-γ. We determined associations between the anti-TIF1-γ index and patient characteristics and disease severities. Sixteen patients with anti-TIF1-γ Ab had concomitant malignancies. A mild positive correlation was found between the levels of serum creatine phosphokinase at the first visit and anti-TIF1-γ levels. In contrast, there was no significant difference in the anti-TIF1-γ Ab index between patients with and without malignancy. Dysphagia tended to be observed in patients with malignancy. On sequential analysis, anti-TIF1-γ levels in patients without malignancy were lower or turned negative after treatment for DM. Ab titers tended to be sustained in patients with stage IV malignancies. Interestingly, a re-increase in the Ab titer was observed on recurrence of malignancy or increase in DM activity. Four patients were completely cured of their malignancies, and anti-TIF1-γ levels in three patients turned negative with the loss of DM activity. These data suggest that higher anti-TIF1-γ titers may not directly indicate the presence of malignancy. Nevertheless, longitudinal changes in the anti-TIF1-γ index in individual patients may partially reflect activities of both DM and malignancy.

Combined immunosuppressive therapy provides favorable prognosis and increased risk of cytomegalovirus reactivation in anti‐melanoma differentiation‐associated gene 5 antibody‐positive dermatomyositis

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) is myositis-specific autoantibody associated with rapidly progressive interstitial lung disease (ILD) and poor prognosis. In this retrospective observational study, we aimed to verify the efficacy and safety of introducing combined immunosuppressive therapy for anti-MDA5 Ab-positive dermatomyositis (DM) from their early stage. We recruited all Japanese patients diagnosed with DM in our clinic between January 2011 and October 2018, who had anti-MDA5 Ab, anti-aminoacyl transfer RNA synthetase Ab or anti-transcriptional intermediary factor 1-γ Ab. Combined immunosuppressive therapy was defined as combination of systemic corticosteroids, i.v. cyclophosphamide and tacrolimus. The difference of clinical features among the three groups was analyzed by multiple comparison analysis. The longitudinal change of the measurements from baseline was examined by Wilcoxon signed-rank test. Association between therapeutic regimens and adverse events was examined by logistic regression analysis. As a result, combined immunosuppressive therapy was most frequently used in the anti-MDA5 Ab-positive group, which significantly improved their forced vital capacity of the lung. Interval time since initial visit until starting treatment was the shortest in the anti-MDA5 Ab-positive group. There was no significant difference in the incidence of death and recurrence among the three groups. Cytomegalovirus reactivation was most common in the anti-MDA5 Ab-positive group, associated with combined immunosuppressive therapy. Collectively, early introduction of combined immunosuppressive therapy was effective for DM patients with anti-MDA5 Ab. At the same time, clinicians should be aware of the risk of cytomegalovirus reactivation during the treatment.

Cancer and Idiopathic Inflammatory Myositis

Here we present an update on best practices and clinical considerations when evaluating IIM patients for malignancy. Idiopathic inflammatory myopathies (IIM) comprise a group of diseases including dermatomyositis (DM), polymyositis (PM), and immune-mediated necrotizing myopathies (IMNM). There is an increased risk of concomitant cancer near the time of myositis onset (cancer-associated myositis, CAM) in unique subsets of IIM patients, particularly those with anti-transcriptional intermediary factor 1-gamma (anti-TIF1-γ), anti-nuclear matrix protein-2 (NXP-2), and potentially anti-3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR) antibodies. While myositis-specific autoantibodies (MSAs) improve risk stratification for cancer in IIM patients, evidenced-based data continues to be lacking with regard to the optimal cancer assessment and duration. Data has been supportive of the association of certain myositis-specific antibodies with malignancy as mentioned above. The optimal strategy for cancer screening remains under discussion but the highest risk of malignancy appears to be within 1 to 3 years of diagnosis making this an important window to maintain vigilance.

Cutaneous manifestations of dermatomyositis characterized by myositis-specific autoantibodies.

Dermatomyositis (DM) is an inflammatory myopathy with characteristic skin manifestations, the pathologies of which are considered autoimmune diseases. DM is a heterogeneous disorder with various phenotypes, including myositis, dermatitis, and interstitial lung disease (ILD). Recently identified myositis-specific autoantibodies have been associated with distinct clinical features. For example, anti-melanoma differentiation-associated protein 5 antibodies have a high specificity for clinically amyopathic DM presenting rapidly progressive ILD. Furthermore, anti-transcriptional intermediary factor 1γ antibodies found in patients with juvenile and adult DM are closely correlated with malignancies, especially in elderly patients. Finally, patients with anti-aminoacyl-transfer RNA synthetase antibodies share characteristic clinical symptoms, including myositis, ILD, arthritis/arthralgia, Raynaud’s phenomenon, and fever; thus, the term “anti-synthetase syndrome” is also used. With a focus on the characteristic cutaneous manifestations in each subgroup classified according to myositis-specific autoantibodies, we introduce the findings of previous reports, including our recent analysis indicating that skin eruptions can be histopathologically classified into myositis-specific autoantibody-associated subgroups and used to determine the systemic pathologies of the different types of antibody-associated DM.

The role of cancer-associated autoantibodies as biomarkers in paraneoplastic myositis syndrome.

The aim of this study is to provide a comprehensive overview of the current insight about the clinical utility of cancer-associated autoantibodies (CAAs) as biomarkers in paraneoplastic myositis syndrome (PMS). In addition, the possible mechanisms of the relationship between malignancy and myositis onset are discussed. It has become increasingly clear that a subgroup of the myositis-specific autoantibodies could be considered as CAAs because they are closely related to the PMS. Increased risk of cancer was found in patients with antitranscriptional intermediary factor 1-γ (TIF1-γ), antinuclear matrix protein-2 (NXP-2), anti3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or antismall ubiquitin-like modifier 1-activating enzyme (SAE) antibodies. However, the diagnosing sensitivity and specificity of these CAAs for PMS are different among different cohort studies. Abnormally expressed or mutated autoantigen genes in tumor could possibly induce cross immunity against self-proteins and subsequently lead to the development of PMS. Anti-TIF1-γ, anti-NXP-2, anti-HMGCR and anti-SAE antibodies may act as CAAs in PMS. It is necessary to closely screen and monitor for cancer in patients with CAAs. The recent studies of the relationship between CAAs and PMS provided important new insights into the disease mechanisms.

Anti-transcriptional intermediary factor 1-γ antibody as a biomarker in patients with dermatomyositis.

The presence of anti-transcriptional intermediary factor (TIF)1-γ antibody (Ab) is associated with cancer in adult patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). In this study, we examined whether anti-TIF1-γ Ab levels are associated with disease activity in patients with CADM/DM. Anti-TIF1-γ Ab levels were examined in 23 patients with CADM or DM (CADM, n=6; DM, n=17). Baseline characteristics and outcomes were recorded, and serial measurements of anti-TIF1-γ Ab levels were obtained. Of the 23 patients with detectable anti-TIF1-γ Ab, 16 (70%) had an internal malignancy, while two (9%) had interstitial lung disease. Mean initial anti-TIF1-γ Ab levels (134±47 index) were significantly decreased after 24months (54±45 index, P<0.0001) and remained decreased thereafter. Anti-TIF1-γ Ab became negative (index value, <32) in 10 patients (43%) and remained positive (index value, ≥32) in 13 patients (57%) during the clinical course. The frequency of remission in the anti-TIF1-γ Ab-negative conversion group (100%) was significantly higher than in the sustained positive group (0%, P<0.0001). Furthermore, mortality in the anti-TIF1-γ Ab-negative conversion group (0%) was significantly lower than that in sustained positive group (69%, P<0.001). This study indicates that anti-TIF1-γ Ab levels are a useful and relevant surrogate marker of disease activity during follow-up monitoring.

Predictive factors for sustained remission with stratification by myositis-specific autoantibodies in adult polymyositis/dermatomyositis.

The aim of this study was to clarify predictive factors for sustained remission in adult patients with PM/DM, particularly focusing on stratification by myositis-specific autoantibodies (MSAs). A total of 162 adult patients with PM/DM who were followed up for >1 year after diagnosis were retrospectively enrolled. MSAs were evaluated comprehensively in 102 patients whose sera were available. Sustained remission was defined as no evidence of disease activity (active skin rash, active myositis or active interstitial lung disease) for longer than a 6-month continuous period while undergoing myositis therapy or no medication. Clinical data were reviewed in patients' medical charts. The sustained remission rate for all patients was 58% during the median follow-up period at 4 years. With regard to MSAs, the achievement rate of sustained remission among MSA-negative patients was significantly higher than that for patients with anti-aminoacyl-tRNA synthetase (P = 0.004), anti-melanoma differentiation-associated gene 5 (P = 0.037) or anti-transcriptional intermediary factor 1-γ (P = 0.013) antibodies. MSA-negative status (odds ratio 5.84, P = 0.009) and absence of severe muscle weakness requiring assistance at diagnosis (odds ratio 43.6, P < 0.001) were independent factors associated with sustained remission in multivariate analysis. Cumulative remission rates were significantly higher (P < 0.001) in patients with both the MSA-negative status and absence of severe muscle weakness at diagnosis than the others. MSA-negative status and the absence of severe muscle weakness requiring assistance at diagnosis are independent predictive factors for sustained remission in adult PM/DM patients.

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

Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibodies are the main predictors of cancer in dermatomyositis (DM). Yet, a substantial proportion of anti-TIF1γ-positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM. This multicenter study was conducted in adult anti-TIF1γ-positive DM patients from August 2013 to August 2017. Anti-TIF1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase (CK) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model. Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years; ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti-TIF1γ IgG2 was significantly associated with mortality (P = 0.0011) and occurrence of cancer during follow-up (P < 0.0001), with a 100% positive predictive value for cancer when the mean fluorescence intensity of anti-TIF1γ IgG2 was >385. None of the patients developed cancer after 24 months of follow-up. Univariate survival analyses showed that mortality was also associated with age >60 years (P = 0.0003), active DM (P = 0.0042), cancer (P = 0.0031), male sex (P = 0.011), and CK level >1,084 units/liter (P = 0.005). Multivariate analysis revealed that age >60 years (P = 0.015) and the presence of anti-TIF1γ IgG2 (P = 0.048) were independently associated with mortality. Our findings indicate that anti-TIF1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti-TIF1γ-positive DM patients.

Clinical characteristics of cancer-associated myositis complicated by interstitial lung disease: a large-scale multicentre cohort study.

To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation-associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.

A Case of Small Cell Lung Cancer with Anti-Transcription Intermediary Factor 1 (TIF1)-γ Antibody-positive Dermatomyositis as Paraneoplastic Syndrome

A Case of Small Cell Lung Cancer with Anti-Transcription Intermediary Factor 1 (TIF1)-γ Antibody-positive Dermatomyositis as Paraneoplastic Syndrome

002 RNA-seq analysis reveals unique transcriptome signatures in dermatomyositis with distinct autoantibodies specificities

To investigate the transcriptional difference between dermatomyositis with distinct autoantibodies. we performed high throughput sequencing technologies in 27 dermatomyositis and 7 healthy volunteers. These dermatomyositis patients were segregated into three subsets based on distinct autoantibodies present in their sera. Including 10 patients that anti-melanoma differentiation associated gene 5 antibody (MDA-5) positive with interstitial lung disease (ILD, and 8 patients that anti-transcriptional intermediary factor 1-γ(TIF1-γ) antibody positive with tumor, and 9 patients that both two antibodies are negative with neither interstitial lung disease nor tumor. We extract RNA from the peripheral blood mononuclear cells of these patients and healthy controls. BGI-seq 500 RS was using for sequencing. Gene ontology analysis and pathway enrichment analysis revealed cytokine activity, receptor binding and protein binding molecular function were specifically dysregulated in MDA5 positive patients. Glycosaminoglycan binding and antioxidant activity were specifically dysregulated in TIF1-γ positive patients. Both patient subsets were compared with antibodies negative patients. We also found different immune pathway between three subsets. Such as innate and adaptive immune system play an important role in the pathogenesis of dermatomyositis. This study has identified unique expression pattern of transcripts in DM patients. This ‘sub-grouping’ approach could further be useful for clinical evaluation of DM patients and devising targeted therapeutics.

The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody-positive dermatomyositis.

Objectives To characterize the 10 year relationship between anti-transcriptional intermediary factor 1 antibody (anti-TIF1-Ab) positivity and cancer onset in a large UK-based adult DM cohort.MethodsData from anti-TIF1-Ab-positive/-negative adults with verified diagnoses of DM from the UK Myositis Network register were analysed. Each patient was followed up until they developed cancer. Kaplan–Meier methods and Cox proportional hazard modelling were employed to estimate the cumulative cancer incidence.ResultsData from 263 DM cases were analysed, with a total of 3252 person-years and a median 11 years of follow-up; 55 (21%) DM cases were anti-TIF1-Ab positive. After 10 years of follow-up, a higher proportion of anti-TIF1-Ab-positive cases developed cancer compared with anti-TIF1-Ab-negative cases: 38% vs 15% [hazard ratio 3.4 (95% CI 2.2, 5.4)]. All the detected malignancy cases in the anti-TIF1-Ab-positive cohort occurred between 3 years prior to and 2.5 years after DM onset. No cancer cases were detected within the following 7.5 years in this group, whereas cancers were detected during this period in the anti-TIF1-Ab-negative cases. Ovarian cancer was more common in the anti-TIF1-Ab-positive vs -negative cohort: 19% vs 2%, respectively (P < 0.05). No anti-TIF1-Ab-positive case <39 years of age developed cancer, compared with 21 (53%) of those ≥39 years of age.ConclusionAnti-TIF1-Ab-positive-associated malignancy occurs exclusively within the 3 year period on either side of DM onset, the risk being highest in those ≥39 years of age. Cancer types differ according to anti-TIF1-Ab status, and this may warrant specific cancer screening approaches.

Anti-TIF1γ antibody and the expression of TIF1γ in idiopathic inflammatory myopathies.

Anti-transcriptional intermediary factor 1 (TIF1) antibody is associated with idiopathic inflammatory myopathies (IIMs). The aim of this study was to investigate the expression of TIF1s in IIMs. TIF1α, β or γ expression in the skin and muscle of patients and controls was studied by immunohistochemistry. Serum myositis-specific autoantibodies were detected by immunoblot. TIF1α was expressed in the skin of most dermatomyositis (DM) patients but not in the controls (80% vs 0%, P<0.001). TIF1β was expressed in all tissues of patients and controls. TIF1γ was expressed in the muscle of DM patients compared to controls (42.1% vs 0%, P=0.039) and associated with tubuloreticular bodies (P=0.003). Anti-TIF1γ was related with TIF1γ expression in the muscle (P=0.042). TIF1α expression in the skin and TIF1γ in the muscle of DM was increased compared to controls. TIF1γ expression in the muscle of IIMs was related to anti-TIF1γ antibody.

New insights in myositis-specific autoantibodies.

The aim of this study was to provide the most recent evidence on clinical utility of myositis-specific autoantibodies (MSAs) in the management of patients with myositis. In the last few years, several evidences have emerged on the clinical and pathogenetic role of established and novel MSA. Antisynthetase antibodies represent a reliable biomarker for pulmonary involvement also in patients with connective tissue diseases other than myositis. Antisignal recognition particle and antihydroxy-3-methylglutaryl coenzyme A reductase autoantibodies are able to induce complement-dependent muscle damage. Dermatomyositis-specific antibodies are useful indicators of clinical diversity. The pivotal role of antitranscription intermediary factor 1γ autoimmune response in adult-age paraneoplastic dermatomyositis has been further asserted. AnticN1A and antifour-and-a-half LIM protein 1 antibodies are newly conceived myositis-related antibody specificities, which can contribute to patients' stratification into more homogeneous groups. Distinct autoantibody-associated clinical phenotypes can be predicted by extended MSA testing in serum. Standardization and validation of MSA laboratory detection methods is strongly recommended for better supporting myositis diagnosis, management and prognosis definition.