Marked Improvement of Anti-TIF1-γ Antibody-Positive Dermatomyositis After Chemoradiotherapy to Relevant Nasopharyngeal Cancer.
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ABSTRACT:
SUBMITTER: Tomita N
PROVIDER: S-EPMC8361053 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesThe objective of the current study was to detect plasma profiles of inflammatory cytokines for determining potential biomarkers indicating cancer presence among the anti-TIF1-γ antibody-positive dermatomyositis (DM) patients.MethodsTwenty-seven cancer-associated anti-TIF1-γ antibody-positive DM (Cancer TIF1-γ-DM) patients were compared with 20 anti-TIF1-γ antibody-positive DM patients without cancer (Non-cancer TIF1-γ-DM) and 10 healthy controls (HC). The plasma levels of 17 cytokines were determined using the Luminex 200 system. The ability of plasma VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ levels to distinguish the presence of cancer was evaluated through the area under the curve (AUC) analysis. Potential protein interactions of TIF1-γ and the five cytokines were analyzed using the STRING database.ResultsVEGF-A, TNF-α, CCL2, IL-6, and IFN-γ plasma levels were significantly higher in the Cancer TIF1-γ-DM group, especially those without any anticancer treatment, than those in the non-cancer TIF1-γ-DM and HC groups. Meanwhile, anti-TIF1-γ antibody and the five cytokines could distinguish cancer presence in anti-TIF1-γ antibody-positive DM patients. The STRING network indicated that TIF1-γ potentially interacted with the cytokines. Positive correlations of VEGF-A among CCL2, IL-6, and IFN-γ and between IFN-γ and IL-6 were observed in Cancer TIF1-γ-DM patients. VEGF-A, TNF-α, CCL2, and IL-6 were positively associated with muscle-associated enzymes among the Cancer TIF1-γ-DM patients.ConclusionThe present study identified VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ as significant potential biomarkers indicating the presence of cancer and demonstrated a more detailed cytokine profile during diagnosis. These biomarkers could provide better screening strategies and insight into the Cancer TIF1-γ-DM pathogenesis. Key Points • VEGF-A, TNF-α, CCL2, IL-6, and IFN-γ are potential biomarkers of cancer in cancer-associated anti-TIF1-γ antibody-positive dermatomyositis. Potential pathogenic molecular mechanism of the cancer-associated anti-TIF1-γ antibody-positive dermatomyositis.
| S-EPMC9935732 | biostudies-literature
Project description:BackgroundThe prevalence of dermatomyositis (DM) versus DM and polymyositis (PM) combined has been shown to be negatively associated with latitude. This observation has been attributed to increasing exposure to ultraviolet (UV) light towards the equator. In this study, we investigated whether differing genetic background in populations could contribute to this distribution of DM.MethodsCase data derived from the MYOGEN (Myositis Genetics Consortium) Immunochip study (n = 1769) were used to model the association of DM prevalence and DM-specific autoantibodies with latitude. Control data (n = 9911) were used to model the relationship of human leucocyte antigen (HLA) associated with DM autoantibodies and DM or PM single-nucleotide polymorphisms (suggestive significance in the Immunochip project, P < 2.25 × 10- 5) in healthy control subjects with latitude. All variables were analysed against latitude using ordered logistic regression, adjusted for sex.ResultsThe prevalence of DM, as a proportion of DM and PM combined, and the presence of anti-transcription intermediary factor 1 (anti-TIF1-γ) autoantibodies were both significantly negatively associated with latitude (OR 0.96, 95% CI 0.95-0.98, P < 0.001; and OR 0.95, 95% CI 0.92-0.99, P = 0.004, respectively). HLA alleles significantly associated with anti-Mi-2 and anti-TIF1-γ autoantibodies also were strongly negatively associated with latitude (OR 0.97, 95% CI 0.96-0.98, P < 0.001 and OR 0.98, 95% CI 0.97-0.99, P < 0.001, respectively). The frequency of five PM- or DM-associated SNPs showed a significant association with latitude (P < 0.05), and the direction of four of these associations was consistent with the latitude associations of the clinical phenotypes.ConclusionsThese results lend some support to the hypothesis that genetic background, in addition to UV exposure, may contribute to the distribution of DM.
| S-EPMC5994128 | biostudies-literature
Project description:We investigate the accumulated microbial and autoantigen antibody repertoire in adult-onset dermatomyositis patients sero-positive for TIF1γ (TRIM33) autoantibodies. We use an untargeted high-throughput approach which combines immunoglobulin disease-specific epitope-enrichment and identification of microbial and human antigens. We observe antibodies recognizing a wider repertoire of microbial antigens in dermatomyositis. Antibodies recognizing viruses and Poxviridae family species are significantly enriched. The identified autoantibodies recognise a large portion of the human proteome, including interferon regulated proteins; these proteins cluster in specific biological processes. In addition to TRIM33, we identify autoantibodies against eleven further TRIM proteins, including TRIM21. Some of these TRIM proteins share epitope homology with specific viral species including poxviruses. Our data suggest antibody accumulation in dermatomyositis against an expanded diversity of microbial and human proteins and evidence of non-random targeting of specific signalling pathways. Our findings indicate that molecular mimicry and epitope spreading events may play a role in dermatomyositis pathogenesis.
| S-EPMC7997983 | biostudies-literature
Project description:ObjectivesStudies concerning myocardial involvement (MI) in patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis/clinically amyopathic dermatomyositis (anti-MDA5 Ab+ DM/CADM) are scarce. We aimed to characterize MI in our anti-MDA5 Ab+ DM/CADM cohort and to investigate its association with prognosis.MethodsIn this single-center retrospective study, anti-MDA5 Ab+ hospitalized DM/CADM patients who underwent transthoracic echocardiography (TTE) were enrolled. Myocardial involvement was diagnosed according to abnormal cardiac structure and function detected by TEE. Clinical features and cardiac examination findings of patients with MI were analyzed. Clinical features, laboratory findings, complications, and treatments were compared between MI and non-MI, deceased, and survival patients. Logistic regression analysis was used to explore the independent risk factors for the occurrence of MI and prognostic factors for these patients.ResultsSeventy-six hospitalized patients with anti-MDA5 Ab+ DM/CADM were enrolled. Twelve (15.8%) patients were diagnosed with MI. Of the 12 patients, three underwent cardiac magnetic resonance imaging (CMR) and late gadolinium enhancement (LGE) were noted for them. TEE revealed that eight (66.7%) patients had left atrial and/or ventricular enlargement, three (25.0%) had cardiac hypertrophy, six (50.0%) had diffuse ventricular wall dyskinesia, and seven (58.3%) had diastolic dysfunction. Six (50.0%) patients with MI developed heart failure (HF) during treatment. Of the 12 patients, one patient died of HF caused by myocarditis, three died of infection, and four died of exacerbation of rapidly progressive interstitial lung disease (RP-ILD). Logistic regression analysis revealed that dysphagia (OR 3.923, 95% CI 1.085, 14.181), NT-proBNP >600 pg/ml (OR 18.333, 95% CI 1.508, 222.875), and increased peripheral white blood cells (OR 1.201, 95% CI 1.003, 1.438) were risk factors for the occurrence of MI, but plasma albumin (OR 0.892, 95% CI 0.796, 0.999) was a protective factor. Both MI (OR 5.984, 95% CI 1.174, 30.496) and RP-ILD (OR 11.875, 95% CI 2.796, 50.411) were independent risk factors for the mortality of these anti-MDA5 Ab+ DM/CADM patients.ConclusionMyocardial involvement is not rare and is an independent poor prognostic factor of anti-MDA5 Ab+ DM/CADM patients. Cardiac abnormality screening is necessary for them.
| S-EPMC9379921 | biostudies-literature
Project description:BackgroundAnti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) has low survival rate, whereas macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases. Their coexistence is very rare. This study aimed to describe the prevalence, clinical characteristics, and outcomes of anti-MDA5 antibodies-positive DM patients complicated with MAS.MethodsIn this retrospective study, we enrolled DM patients with anti-MDA5 antibodies, who were hospitalized between 2016 and 2020 and included patients diagnosed with MAS.ResultsWe identified four (2%) DM patients with anti-MDA5 antibodies. They were females with interstitial lung disease (ILD). The level of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and ferritin were significantly higher in the MAS group than those without MAS (p < 0.05). Patients with MAS were significantly more likely to develop a dysphagia (p = 0.012). Literature review revealed eight similar cases. Together with the present study, we identified 12 patients complicated with ILD. The median age of disease onset was 52 years with a male to female ratio of 1:6. The median duration between DM onset and MAS diagnosis was 3 months. The mortality of MAS in anti-MDA5 antibody-positive DM was 50%. Patients who died were older than those who survived (56.7 years versus 35.5 years; p = 0.015).ConclusionsMAS was rare in anti-MDA5 antibody-positive DM. The higher the level of AST, LDH, and ferritin, the greater the risk of MAS. They were associated with high mortality rates, particularly in older patients.
| S-EPMC9109495 | biostudies-literature
Project description:Anti-melanoma differentiation-associated gene 5 (MDA5) antibody, a dermatomyositis (DM)-specific antibody, is strongly associated with interstitial lung disease (ILD). Patients with idiopathic inflammatory myopathy (IIM) who are anti-MDA5 antibody positive [anti-MDA5 (+)] often experience chest symptoms during the active disease phase. These symptoms are primarily explained by respiratory failure; nevertheless, cardiac involvement can also be symptomatic. Thus, the aim of this study was to investigate cardiac involvement in anti-MDA5 (+) DM. A total of 63 patients with IIM who underwent electrocardiography (ECG) and ultrasound cardiography (UCG) during the active disease phase from 2016 to 2021 [anti-MDA5 (+) group, n = 21; anti-MDA5-negative (-) group, n = 42] were enrolled in the study, and their clinical charts were retrospectively reviewed. The ECG and UCG findings were compared between the anti-MDA5 (+) and anti-MDA5 (-) groups. All anti-MDA5 (+) patients had DM with ILD. The anti-MDA5 (+) group showed more frequent skin ulcerations and lower levels of leukocytes, muscle enzymes, and electrolytes (Na, K, Cl, and Ca) than the anti-MDA5 (-) group. According to the ECG findings obtained during the active disease phase, the T wave amplitudes were significantly lower for the anti-MDA5 (+) group than for the anti-MDA5 (-) group (I, II, and V4-6 lead; p < 0.01; aVF and V3, p < 0.05). However, the lower amplitudes were restored during the remission phase. Except for the E wave, A wave and Sep e', the UCG results showed no significant differences between the groups. Four patients with anti-MDA5 (+) DM had many leads with lower T wave and cardiac abnormalities (heart failure, diastolic dysfunction, myocarditis) on and after admission. Though anti-MDA5 (+) patients clinically improved after immunosuppressive therapy, some of their ECG findings did not fully recover in remission phase. In conclusion, anti-MDA5 (+) DM appears to show cardiac involvement (electrical activity and function) during the active phase. Further studies are necessary to clarify the actual cardiac condition and mechanism of these findings in patients with anti-MDA5 (+) DM.
| S-EPMC8776991 | biostudies-literature
Project description:ObjectiveTo explore the clinical features and prognoses of dermatomyositis (DM) associated with a double-positive anti-MDA5 and anti-aminoacyl-tRNA synthetase (anti-ARS) antibody presentation.MethodsWe retrospectively analyzed 1280 consecutive patients with idiopathic inflammatory myopathy (IIM). Individuals with anti-MDA5 and anti-ARS antibodies (anti-MDA5+/ARS+) were compared to anti-MDA5-/ARS+ and anti-MDA5+/ARS- control individuals based on clinical, pulmonary radiological characteristics, treatment, and follow-up information.ResultsSix individuals (0.47%) presented with anti-MDA5+/ARS+; of these, 2 (33.3%) were anti-PL-12+, 2 (33.3%) were anti-Jo-1+, 1 (16.7%) was anti-EJ+, and 1 (16.7%) was anti-PL-7+. Hallmark cutaneous manifestations, including Gottron's sign (100%), heliotrope rash (50%), mechanic's hand (66.7%), and skin ulcers (16.7%) were common. Anti-MDA5+/ARS+ patients tended to have higher ferritin levels (p = 0.038) than anti-MDA5-/ARS+ group, and higher CD4+ T-cell counts (p = 0.032) compared to the anti-MDA5+/ARS- group. Radiologically, NSIP with OP overlap was predominant (60%). Consolidation (60%), ground-glass attenuation (GGA) (80%), traction bronchiectasis (80%), and intralobular reticulation (100%) were common in anti-MDA5+/ARS+ individuals. All were diagnosed with ILD and 50% were categorized as RPILD. All patients received glucocorticoids combined with one or more immunosuppressants. Most (83.3%) had a good prognosis following treatment, but there was no difference in the survival rate between the three subgroups.ConclusionPresentation with anti-MDA5+/ARS+ DM was rare. The clinical and radiological characteristics of anti-MDA5+/ARS+ DM combined the features of anti-MDA5+ and anti-ARS+ individuals. Individuals with anti-MDA5+/ARS+ antibodies may respond well to glucocorticoid therapy; glucocorticoids combined with one or more immunosuppressants may be considered a basic treatment approach.
| S-EPMC9468482 | biostudies-literature
Project description:Dermatomyositis (DM), a myopathy associated with inflammation and muscle weakness, has historically been difficult to diagnose. Recently, nuclear matrix protein (NXP-2) antibodies have been described as a myositis-specific antibody that may aid in the diagnostic evaluation. We present the case of a 21-year-old, previously healthy, African American male with DM. He presented to our outpatient clinic with periorbital swelling and a rash, for which he was started on prednisone by an ophthalmologist. Towards the end of the prednisone taper, he began to experience muscle weakness, a worsening rash, and dysphagia to solids with a resultant loss of 60 pounds within a month. He was transferred to a tertiary care hospital where he was further evaluated and ultimately diagnosed with dermatomyositis, supported by skin and muscle biopsies, and was found to be positive for NXP-2. He was given intravenous immunoglobulin (IVIG) and high-dose steroids with improvement.
| S-EPMC5485271 | biostudies-other
Project description:BackgroundIdiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM.ObjectivesTo investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies.MethodsIn the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival.ResultsThe prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5+ DM patients it was 7.5/100 person-years and in MDA5- IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5+ DM patients who had a significant decrease in their CD4+ T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5+ DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5+ DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05).ConclusionPJP has an alarming high incidence and mortality in MDA5+ DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5+ DM patients.
| S-EPMC8417987 | biostudies-literature
Project description:Transcriptional regulators play critical roles in the regulation of cell fate during hematopoiesis. Previous studies in zebrafish have identified an essential role for the transcriptional intermediary factor TIF1? in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1? plays a similar role in murine erythropoiesis and to assess its function in other blood lineages, we generated mouse models with hematopoietic deletion of TIF1?. Our results showed a block in erythroid maturation in the bone marrow following tif1? deletion that was compensated with enhanced spleen erythropoiesis. Further analyses revealed a defect in transcription elongation of erythroid genes in the bone marrow. In addition, loss of TIF1? resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1? exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1? plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved.
| S-EPMC3540997 | biostudies-literature