Anti-transcriptional Intermediary Factor Research Articles

A retrospective study for clinical characteristics of 293 patients with dermatomyositis.

This retrospective study aimed to investigate differences in clinical characteristics between different antibody phenotypes in patients with dermatomyositis (DM). Two hundred and ninety-three patients with DM were included in this study from September 2018 to September 2023. We collected basic clinical data from the patients, using statistical methods to analyze the clinical characteristics, and used survival analysis and COX regression to assess the prognosis of the patients. In the 293 patients, the antibody distribution was as follows: antibody negative (50, 20.3%), anti-melanoma differentiation-associated gene 5 (MDA5) antibody (104, 42.3%), anti-transcription intermediary factor γ (TIF-γ) antibody (41, 16.7%), anti-complex nucleosome remodeling histone deacetylase (Mi2) antibody (28, 11.4%), anti-nuclear matrix protein 2 (NXP2) antibody (19, 7.7%), anti-small ubiquitin-like modifier activating enzyme (SAE) antibody (4, 1.6%). Interstitial pneumonia (P < .001), lung infection (P < .001), respiratory symptoms (P < .001), arthralgia (P < .001), and fever (P < .001) were more likely to be seen in patients with anti-MDA5 antibody. Malignancy (P < .001) and V-sign (P = .017) were more likely to occur in anti-TIF1-γ antibody positive patients. Anti-NXP2 antibody-positive patients showed more symptoms of muscle involvement, such as myasthenia (P = .002), myalgia (P = .003) and dysphagia (P = .001). In the analysis of prognosis, age at onset (hazard ratio = 1.096, 95% CI: 1.064-1.129, P < .001), fever (hazard ratio = 2.449, 95% CI: 1.183-5.066, P = .016), γ-glutamyl transferase level (hazard ratio = 1.005, 95% CI: 1.002-1.008, P < .001), eosinophil level (hazard ratio = 0.000, 95% CI: 0.000-0.324, P = .024), and complement 3 (C3) level (hazard ratio = 0.115, 95% CI: 0.023-0.575, P = .008) had a statistically significant effect on survival time. The clinical features of DM are associated with myositis-specific antibodies. At the same time, advanced age, fever, elevated γ-glutamyl transferase levels, and reduced C3 and eosinophil levels may be associated with poor prognosis in patients with DM. These data may provide useful information for clinical management of patients with DM.

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.

Clinical and laboratory features between anti-TIF1γ dermatomyositis with and without malignancy: 37 case series and a review.

We aimed to analyze the clinical profile and malignancy indicators in dermatomyositis (DM) with anti-transcriptional intermediary factor 1 antibody (anti-TIF1γ-Ab). A comparison was made between clinical information of anti-TIF1γ DM patients with and without malignancy. Additionally, a review of the literature on anti-TIF1γ DM and malignancy was conducted by searching PubMed and EMBASE databases. In our cohort of 37 patients, 27.0% (10/37) developed malignancy. The timeframe during which these 10 patients developed malignancy ranged from 21 months prior to the diagnosis of DM to 36 months following the diagnosis of DM. Specifically, one patient was diagnosed with breast cancer at the age of 36. Comparing the groups with and without malignancy, we found that age over 65 years (40% vs 7.4%, P = 0.035), a shorter duration from the onset of symptoms to the diagnosis of DM (2.5 vs 10 months, P = 0.003), and higher erythrocyte sedimentation rate (ESR) levels (23 vs 10 mm/h, P = 0.048) were found to be associated with an increased risk of malignancy. Conversely, the presence of Gottron's papules (63% vs 20%, P = 0.029) may suggest a lower likelihood of malignancy. The literature review revealed that the prevalence of myositis-associated malignancy was 40.7% (340/836), with variations ranging from 19% to 82.9% across different series. In summary, factors such as age over 65 years, a shorter duration between symptom onset and diagnosis of DM, and elevated ESR levels may indicate an increased risk of malignancy in anti-TIF1γ DM patients.

Anti-transcription intermediary factor 1 gamma antibody-associated paraneoplastic dermatomyositis: A case report

Dermatomyositis (DM) is an inflammatory myopathy characterized by distinctive cutaneous manifestations. Recent advancements have led to the identification of a novel myositis-specific autoantibody called anti-transcription intermediary factor 1 gamma (anti-TIF-1-γ) which presents with unique cutaneous manifestations and a heightened risk for malignancy. We report a case of a 55-year-old female who presented with proximal muscle weakness, an erythematous rash over the face, blanching erythema over the nape of the neck, and red-on-white lesions over the chest. She was diagnosed with anti-TIF-1-γ positive DM and found to have a palpable mass in the right breast. Biopsy showed triple negative invasive breast carcinoma no special type (NST) grade 3. She showed poor response to steroids and was referred for cancer staging and treatment. The anti-TIF-1-γ antibody serves as a novel tool to identify a subset of DM patients at high risk for cancer. At present, its role in the prognosis or surveillance of cancer recurrence remains uncertain.

Clinical Images: Anti-transcriptional intermediary factor 1γ-positive dermatomyositis with trismus.

Clinical Images: Anti-transcriptional intermediary factor 1γ-positive dermatomyositis with trismus.

Clinical Features and Immunogenetic Risk Factors Associated With Additional Autoantibodies in Anti-Transcriptional Intermediary Factor 1γ Juvenile-Onset Dermatomyositis.

Novel autoantibody specificities including anti-CCAR1 were recently discovered in adult patients with anti-transcriptional intermediary factor (TIF1)-positive dermatomyositis (DM) and were associated with attenuated cancer emergence. The aims of the present study were to examine whether these autoantibodies occur in patients with juvenile-onset DM (JDM) and to determine their associated features. Sera from 150 patients with anti-TIF1γ autoantibody-positive JDM in a cross-sectional cohort and 90 juvenile healthy controls were assayed for anti-CCAR1, anti-C1Z1, anti-IMMT, anti-TBL1XR1, and anti-Sp4 autoantibodies. Demographics, myositis autoantibodies, clinical features, medications, outcomes, and HLA-DRB1 and HLA-DQA1 alleles were compared between those with and without these autoantibodies. Any one of the anti-TIF1γ-associated autoantibodies was present in 44 patients (29%) overall, including 25 (17%) with anti-Sp4, 22 (15%) with anti-TBL1XR1, 14 (9%) with anti-CCAR1, 2 (1%) with anti-C1Z1, and 2 (1%) with anti-IMMT autoantibodies. These anti-TIF1γ-associated autoantibodies frequently co-occurred. Patients with any of the anti-TIF1γ-associated autoantibodies had less frequent falling (34% [15] vs. 53% [56], P = 0.032) and lower peak muscle enzymes. None of the patients had cancer. Among White patients, HLA-DRB1*03 was protective against an anti-TIF1γ-associated autoantibody (odds ratio 0.20, 95% confidence interval 0.07-0.52). Autoantibodies associated with anti-TIF1γ were found in isolation and in combination among a subset of patients with JDM. Patients with these autoantibodies had less severe muscle disease and were not enriched for HLA-DRB1*03. Additional autoantibodies among patients with positive anti-TIF1γ with JDM likely contribute to the heterogeneity of the anti-TIF1γ serologic subgroup.

Research progress on the dermatomyositis specific autoantibodies and malignancy associated dermatomyositis.

Dermatomyositis (DM) is an autoimmune disease often complicated with malignant tumors. More than 50% of DM patients have myositis specific autoantibodies in their bodies. DM specific autoantibodies [including anti-migration inhibitory factor (Mi)-2 antibody, anti-nuclear matrix protein (NXP)-2 antibody, anti-transcription intermediary factor (TIF) 1-γ antibody, and anti-small ubiquitin like modifier activating enzyme (SAE) antibody] play important roles in the pathogenesis of malignancy associated DM. Revealing the role of DM specific autoantibodies in the development of malignant tumors in DM patients can provide important evidence for accurately assessing the risk of developing malignant tumors in DM patients, and also provide new ideas for clinical diagnosis of DM and precise treatment.

Analytic and Clinical Validity of Myositis-Specific Antibodies by Line-Blot Immunoassay Is Essential.

This study assessed the concordance between line blot (LB) and immunoprecipitation (IP) assays for detecting myositis-specific antibodies (MSAs) in idiopathic inflammatory myopathies (IIMs) and their association with IIM subtypes. One hundred patients with IIM were enrolled, and MSA was detected using LB and IP. The IIM subtypes, including immune-mediated necrotizing myopathy-like, anti-tRNA synthetase syndrome-like, and clinically amyopathic dermatomyositis-like, were clinically diagnosed. The validity and reliability of the LB compared with the IP were evaluated. Optimal cutoff levels for LB were determined using various statistical methods including Cohen κ, Gwet's AC, diagnostic odds ratios, and receiver operating characteristic analysis. Line blot exhibited lower specificity and accuracy than IP in predicting IIM subtypes. Some MSAs performed better at higher LB cutoff values. Anti-signal recognition particle antibodies showed poor performance in predicting the immune-mediated necrotizing myopathy-like subtype using LB. Raising the cutoffs improved the reliability of anti-threonyl-tRNA synthetase and anti-signal recognition particle antibodies. Anti-histidyl-tRNA synthetase antibodies performed well at lower positivity, whereas diagnostic odds ratios increased for anti-transcription intermediary factor 1γ and anti-nuclear matrix protein 2 with higher cutoffs. Inconsistencies between LB and IP have been observed in patients with IIM. Individual optimal cutoffs for MSA by LB correlating with IP were determined. Rheumatologists should consider the differences between LB and IP results when classifying IIM subtypes.

Janus kinase inhibitor for anti-transcription intermediary factor 1-γ positive cancer-associated dermatomyositis.

In this retrospective case series, off-label use of Janus kinase inhibitor rapidly and significantly ameliorated the active cutaneous disease in all five glucocorticoid-resistant patients with cancer-associated dermatomyositis who had anti-transcription intermediary factor 1-γ antibodies, showing a promising steroid-sparing effect and a generally well-tolerated safety profile beyond 1-year follow-up.

A Case in Which Breast Cancer Developed at the Same Time As Dermatomyositis, and the Onset of New Cancer Was Able to Be Predicted by the Exacerbating Skin Symptoms and Parallel Increase in the Anti-TIF1-γ Antibody Levels

Dermatomyositis (DM) is an idiopathic inflammatory myopathy. The incidence of malignancy in DM patients is quite high. Anti-transcription intermediary factor 1-γ (anti-TIF1-γ) antibody is more prevalent in DM patients with malignancy than in those without malignancy. A 70-year-old woman developed hoarseness and difficulty swallowing. A physical examination revealed skin abnormalities. Breast cancer was found in her right breast. She was positive for anti-TIF1-γ antibody. Chemotherapy reduced the tumor size, decreased the anti-TIF1-γ antibody level, and improved her symptoms. About 2.5 years later, however, her skin symptoms worsened, and anti-TIF1-γ antibody levels increased again, and colorectal cancer was found. Treatment with endoscopic mucosal resection (EMR) improved her symptoms again. Our case suggests that the exacerbating skin symptoms and parallel increase in the anti-TIF1-γ antibody level led to the detection of a second cancer after treatment of the first cancer in this case of DM.

Two cases of dermatomyositis associated with neuroendocrine tumors.

Dermatomyositis is an idiopathic inflammatory myopathy with cutaneous manifestations, which is associated with several types of malignancies, yet it has been rarely linked to neuroendocrine tumors (NETs). Here we report two cases of dermatomyositis associated with NETs of differing primary sites. Case 1: A 46-year-old female presented with a facial rash and proximal muscle weakness of both extremities. Investigations revealed elevated creatine kinase (CK) and positive anti-transcriptional intermediary factor 1-γ antibody (TIF1γ). The patient had been diagnosed with dermatomyositis and underwent a total body CT scan, which revealed prominent mediastinal lymphadenopathy, which a subsequent biopsy determined to be neuroendocrine carcinoma of small cell type. Treatment with high-dose corticosteroids was initiated, in addition to chemotherapy-based oncological management. Case 2: A 54-year-old female presented with a facial rash, progressive dyspnea, and general malaise. Laboratory investigations revealed positive anti-melanoma differentiation-associated gene-5(MDA5) and positive anti-Ro antibody, with a normal level of creatine kinase (CK). A chest CT scan revealed multiple ground-glass opacities. Despite treatment with high-dose intravenous methylprednisolone, IVIG and an infusion of the anti-IL-6 sarilumab [Kevzara], the patient rapidly deteriorated and was intubated. Within days, the patient developed bowel ischemia and underwent a laparotomy which was then complicated by an invasive infection. This resulted in patient's death. Pathology results from colonic tissue demonstrated an appendiceal neuroendocrine tumor. These cases demonstrate the heterogeneity and complexity of dermatomyositis in association with neuroendocrine tumors.

Autoantibodies Recognizing Specificity Protein 4 Co-occur With Anti-Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis.

Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti-Sp4 autoantibodies co-occurred in patients with anti-transcription intermediary factor 1 (anti-TIF1) autoantibody-positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti-Sp4 autoantibodies in juvenile-onset IIM were investigated. Serum samples from 336 patients with juvenile myositis in a cross-sectional cohort and 91 healthy controls were screened for anti-Sp4 autoantibodies using enzyme-linked immunosorbent assay. Clinical characteristics, outcomes, and HLA alleles of those with and those without anti-Sp4 autoantibodies were compared. Anti-Sp4 autoantibodies were present in 23 patients (7%) with juvenile myositis and were not present in any of the controls. Anti-Sp4 autoantibodies were found among each clinical myositis subgroup. The frequency of TIF1 autoantibody positivity was significantly higher among those with anti-Sp4 autoantibodies (21 [91%] versus 92 [30%], P < 0.001). In the anti-TIF1 autoantibody-positive subgroup, Raynaud's phenomenon (8 [38%] versus 2 [2%], P < 0.001) was more common and peak aspartate aminotransferase was significantly lower in those with anti-Sp4 autoantibodies. None of the patients with anti-Sp4 autoantibodies required a wheelchair. Among White patients, DQA1*04 and DRB1*08 were associated with anti-Sp4 autoantibodies. Anti-Sp4 autoantibodies were found in patients with juvenile-onset IIM, predominantly those with coexisting anti-TIF1 autoantibodies. Patients with anti-Sp4 autoantibodies represent a phenotypic subset of anti-TIF1 autoantibody-positive myositis characterized by frequent Raynaud's phenomenon and less pronounced muscle involvement, similar to adults with these autoantibodies. Novel immunogenetic risk factors for White patients with IIM were identified among juveniles with anti-Sp4 autoantibodies.

Dermatomyositis

Dermatomyositis is a heterogeneous disorder that can be classified into more homogeneous subsets. Autoantibodies are a useful tool in identifying such subsets because they correlate strongly with clinical phenotypes. In dermatomyositis, five disease-specific autoantibodies have been established to date, including antiMi-2, anti-melanoma differentiation-associated gene 5, anti-transcriptional intermediary factor 1, anti-nuclear matrix protein 2, anti-transcriptional intermediary factor 1, and anti-small-ubiquitin-like activating enzyme antibodies. In addition, several novel autoantibodies have recently been demonstrated in patients with dermatomyositis, including anti-four-and-a-half-LIM-domain 1, anti-cell division cycle and apoptosis regulator protein 1, anti-specificity protein 4, anti-cortactin, and IgM anti-angiotensin converting enzyme 2 antibodies.

Anti-transcriptional intermediary factor 1γ antibody-positive dermatomyositis with intravascular lymphoma.

Anti-transcriptional intermediary factor 1γ antibody-positive dermatomyositis with intravascular lymphoma.

Serum level of galectin-9 as a potential biomarker for high risk of malignancy in dermatomyositis.

Galectin-9, as immune checkpoint protein, plays a role in regulating autoimmunity and tumour immunity. Therefore, we explored the pathophysiological link between galectin-9 and malignancy in cancer-related DM (CRDM). Serum galectin-9 were quantified via enzyme-linked immunosorbent assay, and its association with serological indices was evaluated using Spearman analysis. Receiver operating characteristic (ROC) analysis was utilized to determine the cut-off value of galectin-9. Serum levels of galectin-9 were significantly higher in DM patients [23.38 (13.85-32.57) ng/ml] than those in healthy controls (HCs) [6.81 (5.42-7.89) ng/ml, P < 0.0001], and were positively correlated with the cutaneous dermatomyositis disease area severity index activity (CDASI-A) scores (rs=0.3065, P = 0.0172). DM patients with new-onset and untreated cancer (new-CRDM) [31.58 (23.85-38.84) ng/ml] had higher levels of galectin-9 than those with stable and treated cancer (stable-CRDM) [17.49 (10.23-27.91) ng/ml, P = 0.0288], non-cancer-related DM (non-CRDM) [21.05 (11.97-28.02) ng/ml, P = 0.0258], and tumour patients without DM [7.46 (4.90-8.51) ng/ml, P < 0.0001]. Serum galectin-9 levels significantly decreased [27.79 (17.04-41.43) ng/ml vs 13.88 (5.15-20.37) ng/ml, P = 0.002] after anti-cancer treatment in CRDM patients. The combination of serum galectin-9 and anti-transcriptional intermediary factor 1-γ (anti-TIF1-γ) antibody (AUC = 0.889, 95% CI 0.803-0.977) showed the highest predictive value for the presence of cancer in DM. Increased galectin-9 levels were related to tumor progression in CRDM, and galectin-9 was downregulated upon cancer treatment. Monitoring serum galectin-9 levels and anti-TIF1-γ antibodies might be an attractive strategy to achieve tumour diagnosis and predict CRDM outcome.

Association of Anti-CCAR1 Autoantibodies With Decreased Cancer Risk Relative to the General Population in Patients With Anti-Transcriptional Intermediary Factor 1γ-Positive Dermatomyositis.

To describe the disease specificity, clinical phenotype, and risk of cancer in dermatomyositis (DM) patients with autoantibodies against cell division cycle and apoptosis regulator protein 1 (anti-CCAR1). The frequency of anti-CCAR1 autoantibodies was measured by enzyme-linked immunosorbent assay in the serum of DM patients from 2 independent cohorts (Johns Hopkins and Stanford), with patients with several other rheumatic diseases and healthy controls used as comparators. Clinical features and the risk of cancer incidence relative to that in the general population were determined in anti-CCAR1-positive DM patients. Anti-CCAR1 antibodies were significantly associated with anti-transcriptional intermediary factor 1γ (anti-TIF1γ) antibodies present in the serum of patients with DM: 80 (32%) of 252 anti-TIF1γ-positive DM patients versus 14 (8%) of 186 anti-TIF1γ-negative DM patients were positive for anti-CCAR1 antibodies (P < 0.001). Anti-CCAR1 antibodies were not detected in any of the 32 serum samples from healthy controls, and were present at very low frequencies in the sera of patients with other rheumatic diseases: 1 (2.3%) of 44 patients with anti-hydroxymethylglutaryl-coenzyme A reductase-positive necrotizing myopathy, 1 (2.3%) of 44 patients with inclusion body myositis, and 3 (6.5%) of 46 patients with systemic lupus erythematosus were positive for anti-CCAR1 antibodies. Upon examining data on occurrence of cancer from the onset of DM onward, the observed number of cancers diagnosed in anti-TIF-1γ-positive DM patients was significantly greater than expected in both cohorts, with a standardized incidence ratio (SIR) of 3.49 (95% confidence interval [95% CI] 2.39-4.92) in the Johns Hopkins cohort and a SIR of 4.54 (95% CI 3.04-6.52) in the Stanford cohort (each P < 0.001). DM patients who were both anti-TIF1γ positive and anti-CCAR1 positive had lower SIRs for cancer, with a SIR of 1.78 (95% CI 0.77-3.51) (P=0.172) in the Johns Hopkins cohort and a SIR of 1.61 (95% CI 0.44-4.13) (P=0.48) in the Stanford cohort. Anti-CCAR1 autoantibodies are specific for anti-TIF1γ-positive DM. Their presence in anti-TIF1γ-positive patients attenuates the risk of cancer to a level comparable to that seen in the general population.

Diagnostic Yield of Computed Tomography for Cancer Detection in a Tertiary Referral Population of Idiopathic Inflammatory Myositis Patients.

To inform guidance for cancer detection in patients with idiopathic inflammatory myopathy (IIM), we evaluated the diagnostic yield of computed tomography (CT) imaging for cancer screening/surveillance within distinct IIM subtypes and myositis-specific autoantibody strata. We conducted a single-center, retrospective cohort study in IIM patients. Overall diagnostic yield (number of cancers diagnosed/number of tests performed), percentage of false positives (number of biopsies performed not leading to cancer diagnosis/number of tests performed), and test characteristics were determined on CT of the chest and abdomen/pelvis. Within the first 3 years since IIM symptom onset, a total of 9 of 1,011 (0.9%) chest CT scans and 12 of 657 (1.8%) abdomen/pelvis CT scans detected cancer. Diagnostic yields for both CT of the chest and CT of the abdomen/pelvis were highest in dermatomyositis, specifically anti-transcription intermediary factor 1γ (2.9% and 2.4% for CT of the chest and abdomen/pelvis, respectively). The highest percentage of false positives was in patients with antisynthetase syndrome (ASyS) (4.4%) and immune-mediated necrotizing myopathy (4.4%) on CT of the chest, and ASyS (3.8%) on CT of the abdomen/pelvis. Patients ages <40 years old at IIM onset had both low diagnostic yields (0% and 0.5%) and high false-positive rates (1.9% and 4.4%) for CT of the chest and abdomen/pelvis, respectively. In a tertiary referral cohort of IIM patients, CT imaging has a wide range of diagnostic yield and frequency of false positives for contemporaneous cancer. These findings suggest that cancer detection strategies targeted according to IIM subtype, autoantibody positivity, and age may maximize cancer detection while minimizing the harms and costs of over-screening.

060 Appropriate therapeutic target of cancer-associated dermatomyositis with anti-transcriptional intermediary factor 1-γ antibody

060 Appropriate therapeutic target of cancer-associated dermatomyositis with anti-transcriptional intermediary factor 1-γ antibody

In-depth proteomic analysis of juvenile dermatomyositis serum reveals protein expression associated with muscle-specific autoantibodies.

The clinical symptoms and complications of juvenile dermatomyositis (JDM) differ depending on the type of muscle-specific autoantibodies (MSAs) present. We aimed to identify protein expression profiles specific for MSAs that characterize various clinical features by comprehensively analyzing the proteins present in the serum of patients with JDM. We analyzed sera from patients with JDM that were positive for anti-melanoma differentiation-associated protein 5 (MDA5) antibodies (n = 5), anti-nuclear matrix protein 2 (NXP2) antibodies (n = 5), and anti-transcriptional intermediary factor 1 alpha or gamma subunit (TIF1-γ) antibodies (n = 5) and evaluated healthy controls (n = 5) via single-shot liquid chromatography-tandem mass spectrometry (MS) in data-independent acquisition mode, which is superior for comparative quantitative analysis. We identified different protein groups based on MSAs and performed pathway analysis to understand their characteristics. We detected 2,413 proteins from serum MS analysis; 508 proteins were commonly altered in MSAs, including many myogenic enzymes and interferon-regulated proteins. Pathway analysis using the top 50 proteins that were upregulated in each MSA group revealed that the type 1 interferon and proteasome pathways were significantly upregulated in the anti-MDA5 antibody group alone. Although JDM serum contains many proteins commonly altered in MSAs, the pathways associated with clinical features of MSAs differ based on protein accumulation. In-depth serum protein profiles associated with MSAs may be useful for developing therapeutic target molecules and biomarkers.

Association of the serum IgG glycosylation with disease activity of anti-transcription intermediary factor 1 gamma positive dermatomyositis.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterised by the presence of a variety of myositis-specific autoantibodies (MSA) in the circulation. As one of the commonly-detected MSA, anti-transcription intermediary factor 1 gamma (TIF1γ) autoantibody is strongly associated with DM-related malignancy and disease activity. We investigated the glycosylation patterns of serum IgG and to determine the clinical significance of specific glycosylation patterns in patients with anti-TIF1γ positive DM. Lectin microarray was used to reveal the glycosylation patterns of serum IgG among 52 DM, 46 disease controls (DC) and 49 healthy controls (HC). Lectin blot was used to further validate the specific alteration of glycosylation. The correlation between glycan levels and clinical features was also evaluated. The results of lectin microarray showed that compared with the DC group, the DM group had significantly lower glycan levels of mannose and glucose. Compared with the HC group, the glycans levels of GalNAc, galactose, Galβ3GalNAc, sialic acid, and fucose were observed significantly higher in DM group. Lectin blot demonstrated that anti-TIF1γ positive DM had lower glycan level of GlcNAc (recognized by LEL) compared to patients with MSA negative DM, DC, and HC groups. Additionally, the glycan level of GlcNAc was positively associated with manual muscle test (r=0.547, p=0.028), or negatively associated with IL-6 level (r=-0.756, p=0.049) and disease activity score (r=-0.507, p=0.045). Anti-TIF1γ positive DM presents a unique glycosylation pattern in serum IgG. Considering that the glycan level of GlcNAc reflects the inflammatory state and disease activity, glycosylation has a role in clinical utility by monitoring disease in patients with anti-TIF1γ positive DM.