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1.
Front Immunol ; 12: 773352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745149

RESUMO

Anti-MDA5 dermatomyositis is a rare systemic autoimmune disease, historically described in Japanese patients with clinically amyopathic dermatomyositis and life-threatening rapidly progressive interstitial lung disease. Subsequently, the complete clinical spectrum of the disease was enriched by skin, articular and vascular manifestations. Depending on the predominance of these symptoms, three distinct clinical phenotypes with different prognosis are now defined. To date, the only known molecular component shared by the three entities are specific antibodies targeting MDA5, a cytosolic protein essential for antiviral host immune responses. Several biological tools have emerged to detect these antibodies, with drawbacks and limitations for each of them. However, the identification of this highly specific serological marker of the disease raises the question of its role in the pathogenesis. Although current knowledge on the pathogenic mechanisms that take place in the disease are still in their enfancy, several lines of evidence support a central role of interferon-mediated vasculopathy in the development of skin and lung lesions, as well as a possible pathogenic involvement of anti-MDA5 antibodies. Here, we review the clinical and biological evidences in favor of these hypothesis, and we discuss the contribution of emerging therapies that shed some light on the pathogenesis of the disease.


Assuntos
Autoanticorpos/imunologia , Vasos Sanguíneos/patologia , Dermatomiosite/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/imunologia , Pele/patologia , Animais , Dermatomiosite/terapia , Humanos , Interferons/metabolismo , Doenças Pulmonares Intersticiais/terapia , Fenótipo
2.
Sci Rep ; 11(1): 17070, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34426622

RESUMO

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated interstitial lung disease (MDA5+ DM-ILD) is a life-threatening disease. This study aimed to develop a novel pulmonary CT visual scoring method for assessing the prognosis of the disease, and an artificial intelligence (AI) algorithm-based analysis and an idiopathic pulmonary fibrosis (IPF)-based scoring were conducted as comparators. A retrospective cohort of hospitalized patients with MDA5+ DM-ILD was analyzed. Since most fatalities occur within the first half year of the disease course, the primary outcome was the six-month all-cause mortality since the time of admission. A ground glass opacity (GGO) and consolidation-weighted CT visual scoring model for MDA5+ DM-ILD, namely 'MDA5 score', was then developed with C-index values of 0.80 (95%CI 0.75-0.86) in the derivation dataset (n = 116) and 0.84 (95%CI 0.71-0.97) in the validation dataset (n = 57), respectively. While, the AI algorithm-based analysis, namely 'AI score', yielded C-index 0.78 (95%CI 0.72-0.84) for the derivation dataset and 0.77 (95%CI 0.64-0.90) for the validation dataset. These findings suggest that the newly derived 'MDA5 score' may serve as an applicable prognostic predictor for MDA5+ DM-ILD and facilitate further clinical trial design. The AI based CT quantitative analysis provided a promising solution for ILD evaluation.


Assuntos
Dermatomiosite/complicações , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Inteligência Artificial , Dermatomiosite/imunologia , Feminino , Humanos , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Prognóstico
3.
Curr Rheumatol Rep ; 23(8): 63, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-34216297

RESUMO

PURPOSE: Myositis as a rare manifestation of COVID-19 is only recently being reported. This review examines the current literature on COVID-19-induced myositis focusing on etiopathogenesis, clinical presentations, diagnostic practices, and therapeutic challenges with immunosuppression, and the difficulties experienced by rheumatologists in established myositis in the COVID-19 era. RECENT FINDINGS: COVID-19 is associated with a viral myositis attributable to direct myocyte invasion or induction of autoimmunity. COVID-19-induced myositis may be varied in presentation, from typical dermatomyositis to rhabdomyolysis, and a paraspinal affliction with back pain. It may or may not present with acute exponential elevations of enzyme markers such as creatine kinase (CK). Virus-mediated muscle inflammation is attributed to ACE2 (angiotensin-converting enzyme) receptor-mediated direct entry and affliction of muscle fibers, leading on to innate and adaptive immune activation. A greater recognition of the stark similarity between anti-MDA5-positive myositis with COVID-19 has thrown researchers into the alley of exploration - finding common etiopathogenic basis as well as therapeutic strategies. For patients with established myositis, chronic care was disrupted during the pandemic with several logistic challenges and treatment dilemmas leading to high flare rates. Teleconsultation bridged the gap while ushering in an era of patient-led care with the digital transition to tools of remote disease assessment. COVID-19 has brought along greater insight into unique manifestations of COVID-19-related myositis, ranging from direct virus-induced muscle disease to triggered autoimmunity and other etiopathogenic links to explore. A remarkable shift in the means of delivering chronic care has led patients and caregivers worldwide to embrace a virtual shift with teleconsultation and opened doorways to a new era of patient-led care.


Assuntos
COVID-19/fisiopatologia , Miosite/fisiopatologia , Rabdomiólise/fisiopatologia , Imunidade Adaptativa/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Autoanticorpos/imunologia , Dor nas Costas/etiologia , COVID-19/complicações , COVID-19/imunologia , COVID-19/metabolismo , Creatina Quinase/metabolismo , Dermatomiosite/etiologia , Dermatomiosite/imunologia , Dermatomiosite/metabolismo , Dermatomiosite/fisiopatologia , Humanos , Imunidade Inata/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Miastenia Gravis/etiologia , Miastenia Gravis/imunologia , Miastenia Gravis/metabolismo , Miastenia Gravis/fisiopatologia , Miosite/etiologia , Miosite/imunologia , Miosite/metabolismo , Músculos Paraespinais/fisiopatologia , Receptores de Coronavírus/metabolismo , Rabdomiólise/etiologia , Rabdomiólise/imunologia , Rabdomiólise/metabolismo , SARS-CoV-2
7.
Sci Rep ; 11(1): 9821, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972636

RESUMO

To develop a machine learning (ML) model that predicts disease groups or autoantibodies in patients with idiopathic inflammatory myopathies (IIMs) using muscle MRI radiomics features. Twenty-two patients with dermatomyositis (DM), 14 with amyopathic dermatomyositis (ADM), 19 with polymyositis (PM) and 19 with non-IIM were enrolled. Using 2D manual segmentation, 93 original features as well as 93 local binary pattern (LBP) features were extracted from MRI (short-tau inversion recovery [STIR] imaging) of proximal limb muscles. To construct and compare ML models that predict disease groups using each set of features, dimensional reductions were performed using a reproducibility analysis by inter-reader and intra-reader correlation coefficients, collinearity analysis, and the sequential feature selection (SFS) algorithm. Models were created using the linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), support vector machine (SVM), k-nearest neighbors (k-NN), random forest (RF) and multi-layer perceptron (MLP) classifiers, and validated using tenfold cross-validation repeated 100 times. We also investigated whether it was possible to construct models predicting autoantibody status. Our ML-based MRI radiomics models showed the potential to distinguish between PM, DM, and ADM. Models using LBP features provided better results, with macro-average AUC values of 0.767 and 0.714, accuracy of 61.2 and 61.4%, and macro-average recall of 61.9 and 59.8%, in the LDA and k-NN classifiers, respectively. In contrast, the accuracies of radiomics models distinguishing between non-IIM and IIM disease groups were low. A subgroup analysis showed that classification models for anti-Jo-1 and anti-ARS antibodies provided AUC values of 0.646-0.853 and 0.692-0.792, with accuracy of 71.5-81.0 and 65.8-78.3%, respectively. ML-based TA of muscle MRI may be used to predict disease groups or the autoantibody status in patients with IIM and is useful in non-invasive assessments of disease mechanisms.


Assuntos
Dermatomiosite/diagnóstico , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Músculos/diagnóstico por imagem , Polimiosite/diagnóstico , Adulto , Idoso , Anticorpos Antinucleares/análise , Anticorpos Antinucleares/imunologia , Antígenos Ly/imunologia , Biópsia , Dermatomiosite/imunologia , Dermatomiosite/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Músculos/imunologia , Músculos/patologia , Polimiosite/imunologia , Polimiosite/patologia , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ativador de Plasminogênio Tipo Uroquinase/imunologia
8.
Dermatol Online J ; 27(4)2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33999578

RESUMO

We present a patient with anti-MDA5 negative, anti-Ku positive clinically amyopathic dermatomyositis (CADM). A 61-year-old woman presented with a chief complaint of a 20-year history of a pruritic rash that was active on her face, chest, hands, legs, and back. A mildly scaly, erythematous, photo-distributed eruption along with slightly violaceous, scaly papules accentuated on the wrist, metacarpophalangeal joints, proximal interphalangeal and distal interphalangeal joints. Antibody profile was significant for positive ANA and anti-dsDNA, elevated anti-TIF-1gamma (RDL)/p155, and weakly positive anti Ku. Biopsy was consistent with dermatomyositis. Melanoma differentiation-associated gene 5 antibody (anti-MDA-5) has been identified as the most commonly associated autoantibody found in CADM and is associated with poor prognosis and a biomarker for the diagnosis of rapidly progressive interstitial lung disease. To our knowledge, our patient is the first case of negative anti-MDA-5 and anti-Ku positive CADM.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Dermatomiosite/imunologia , Helicase IFIH1 Induzida por Interferon/imunologia , Autoantígeno Ku/imunologia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/patologia , Feminino , Humanos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade
9.
Clin Dermatol ; 39(1): 56-63, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33972054

RESUMO

Autoimmune connective tissue diseases are a heterogeneous group of clinical entities sharing a common feature-an impairment of structural components like collagen and elastin, arising by autoimmune mechanisms. Because most patients are on a long-term immunosuppressive therapy, which renders them vulnerable to infections, a new challenge appears in front of physicians in the coronavirus disease 2019 (COVID-19) era. Immune mechanisms are substantial for the control and ceasing of viral infections, and their impairment may cause serious complications; however, data from immunosuppressed transplant patients do not reveal a higher frequency or diseases' severity in those infected by COVID-19. Several immunotherapies used to treat autoimmune connective tissue diseases favorably modulate the immune response of severe acute respiratory syndrome coronavirus (SARS-CoV-2)-infected patients. The present review highlights the problems of susceptibility, severity, and therapeutic options in patients with autoimmune connective tissue diseases during the COVID-19 pandemic. The relationship between autoimmune connective tissue diseases and COVID-19 infection is explained with antiviral protection genes expression, hypercytokinemia, and lymphohistiocytosis/macrophage activation mechanisms. Recommendations concerning therapy for prevention during the pandemic period or in case of concomitant COVID-19 infection are also presented. Clinical trials are ongoing regarding COVID-19 therapy blocking the cytokine response. © 2021 Elsevier Inc. All rights reserved.


Assuntos
COVID-19/complicações , Dermatomiosite , Lúpus Eritematoso Sistêmico , Escleroderma Sistêmico , Vasculite , Anticorpos Monoclonais Humanizados/uso terapêutico , Antimaláricos/uso terapêutico , COVID-19/epidemiologia , Dermatomiosite/complicações , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Suscetibilidade a Doenças , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Gravidade do Paciente , SARS-CoV-2 , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/imunologia , Tromboembolia/etiologia , Vasculite/tratamento farmacológico
10.
Ann Rheum Dis ; 80(9): 1201-1208, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33811031

RESUMO

OBJECTIVES: To investigate whether autoimmunity to transcriptional intermediary factor 1 (TIF1)γ, a ubiquitous nuclear autoantigen for myositis-specific autoantibodies detected in patients with dermatomyositis (DM) is pathogenetic for inflammatory myopathy. METHODS: Wild-type, ß2-microglobulin-null, perforin-null, Igµ-null and interferon α/ß receptor (IFNAR)-null mice were immunised with recombinant human TIF1γ whole protein. A thymidine incorporation assay was performed using lymph node T cells from TIF1γ-immunised mice. Plasma was analysed using immunoprecipitation followed by western blot analysis and enzyme-linked immunosorbent assays. Femoral muscles were histologically and immunohistochemically evaluated. CD8+ or CD4+ T cells isolated from lymph node T cells or IgG purified from plasma were adoptively transferred to naïve mice. TIF1γ-immunised mice were treated with anti-CD8 depleting antibody and a Janus kinase inhibitor, tofacitinib. RESULTS: Immunisation with TIF1γ-induced experimental myositis presenting with necrosis/atrophy of muscle fibres accompanied by CD8+ T cell infiltration successfully in wild-type mice, in which TIF1γ-specific T cells and antihuman and murine TIF1γ IgG antibodies were detected. The incidence and severity of myositis were significantly lower in ß2-microglobulin-null, perforin-null, CD8-depleted or IFNAR-null mice, while Igµ-null mice developed myositis normally. Adoptive transfer of CD8+ T cells induced myositis in recipients, while transfer of CD4+ T cells or IgG did not. Treatment with tofacitinib inhibited TIF1γ-induced myositis. CONCLUSIONS: Here we show that TIF1γ is immunogenic enough to cause experimental myositis, in which CD8+ T cells and type I interferons, but not CD4+ T cells, B cells or antibodies, are required. This murine model would be a tool for understanding the pathologies of DM.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Dermatomiosite/imunologia , Modelos Animais de Doenças , Camundongos , Doença Autoimune do Sistema Nervoso Experimental/imunologia , Fatores de Transcrição/imunologia , Transferência Adotiva , Animais , Linfócitos T CD4-Positivos/transplante , Linfócitos T CD8-Positivos/transplante , Humanos , Imunização , Imunoglobulina G/imunologia , Cadeias mu de Imunoglobulina/genética , Inibidores de Janus Quinases/farmacologia , Camundongos Knockout , Perforina/genética , Piperidinas/farmacologia , Pirimidinas/farmacologia , Receptor de Interferon alfa e beta/genética , Linfócitos T/imunologia , Microglobulina beta-2/genética
12.
Rinsho Shinkeigaku ; 61(4): 258-261, 2021 Apr 21.
Artigo em Japonês | MEDLINE | ID: mdl-33762494

RESUMO

We report a 47-year-old woman who presented with progressive myalgia, weakness in the proximal limbs, and dysphagia for a month and a half. No skin rash was observed on admission. Examination of MRI data suggested inflammatory changes in the proximal limbs and trunk muscles. Biopsy specimens from the left biceps muscle showed no perifascicular atrophy, but immunohistochemical staining revealed the presence of myxovirus resistance protein A (MxA) in myofibers, strongly suggesting dermatomyositis (DM). In addition, her serum was positive for anti-nuclear matrix protein 2 (anti-NXP-2) antibody, which is reportedly useful as a marker of DM without skin lesions. Her symptoms gradually improved upon intravenous methylprednisolone pulse therapy in conjunction with oral prednisolone, oral tacrolimus, and intravenous immunoglobulin therapy. Our findings suggest that in cases where inflammatory muscle disease is suspected, anti-NXP-2 antibody analyses should be considered for precise diagnosis, even if there are no dermatological symptoms.


Assuntos
Adenosina Trifosfatases/imunologia , Anticorpos Antinucleares/metabolismo , Proteínas de Ligação a DNA/imunologia , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , Doenças Assintomáticas , Biomarcadores/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Proteínas de Resistência a Myxovirus/metabolismo
13.
J Invest Dermatol ; 141(8): 1906-1914.e2, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33675790

RESUMO

Dermatomyositis pathogenesis remains incompletely understood; however, recent work suggests a predominant IFN-1 response. We explored dermatomyositis pathogenesis by quantifying the inflammatory cells in the skin, comparing myeloid with plasmacytoid dendritic cell release of IFN-ß, and assessing myeloid dendritic cell (mDC) contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell-type expression in lesional skin biopsies from 12 patients with moderate-to-severe cutaneous dermatomyositis. Immunofluorescence, laser-capture microdissection, and flow cytometry were used to assess mDC release of IFN-ß in lesional skin biopsies and blood of patients with dermatomyositis. Immunohistochemistry was utilized to determine whether myeloid or plasmacytoid dendritic cells were increased in hydroxychloroquine nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional skin of patients with dermatomyositis. mDCs colocalized with IFN-ß by immunofluorescence and laser-capture microdissection revealed increased IFN-ß mRNA expression by mDCs in lesional skin of patients with dermatomyositis. In blood, both mDCs and plasmacytoid dendritic cells were major producers of IFN-ß in patients with dermatomyositis, whereas plasmacytoid dendritic cells predominately released IFN-ß in healthy controls (P < 0.01). mDCs were significantly increased in the skin of hydroxychloroquine nonresponders compared with that in the skin of responders (P < 0.05). mDCs cells appear to play an important role in dermatomyositis pathogenesis and IFN-ß production.


Assuntos
Células Dendríticas/imunologia , Dermatomiosite/imunologia , Hidroxicloroquina/farmacologia , Interferon beta/metabolismo , Idoso , Biópsia , Células Dendríticas/metabolismo , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia
14.
Biochem Biophys Res Commun ; 551: 155-160, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33740622

RESUMO

OBJECTIVES: Clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by low-grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (RP-ILD) and skin ulcers with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is thought to function as an inhibitor of tumours and inflammation. Here, we aimed to investigate the roles of BATF2 in Th cell differentiation of CADM with an anti-MDA5 autoantibody (anti-MDA5+ CADM). METHODS: Naive CD4+ T cells from human peripheral blood mononuclear cells (PBMCs) of healthy controls (HCs) were isolated and then cultured with IL-12, TGF-ß or TGF-ß plus IL-6 following anti-CD3 and anti-CD28 stimulations. The expression of BATF2 was measured by real-time PCR. The percentages of Th1, Th17 and Treg CD4+ T cells were detected by flow cytometry. BATF2 knockdown of CD4+ T cells was performed using small interfering RNAs (siRNAs). RESULTS: The expression of BATF2 in PBMCs was higher in anti-MDA5+ CADM patients than in healthy controls. The BATF2 mRNA expression was increased under Th1 and Treg polarization but decreased under Th17 polarization. Th17 cell activation-associated genes were possibly increased while Th1 and Treg cell differentiation-associated genes were inhibited by posttranscriptional gene silencing of BATF2 in CD4+ T cells. CONCLUSIONS: BATF2 promoted Th1 and Treg cell differentiation but suppressed Th17 cell activation in anti-MDA5+ CADM.


Assuntos
Autoanticorpos/imunologia , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Linfócitos T CD4-Positivos/imunologia , Dermatomiosite/imunologia , Dermatomiosite/metabolismo , Imunidade Celular , Helicase IFIH1 Induzida por Interferon/imunologia , Proteínas Supressoras de Tumor/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular , Feminino , Humanos , Masculino , RNA Mensageiro/análise , RNA Mensageiro/genética , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Células Th1/citologia , Células Th1/imunologia , Células Th17/citologia , Células Th17/imunologia , Proteínas Supressoras de Tumor/genética , Regulação para Cima
15.
Commun Biol ; 4(1): 419, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772100

RESUMO

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.


Assuntos
Autoanticorpos/imunologia , Dermatomiosite/imunologia , Fatores de Transcrição/imunologia , Autoanticorpos/genética , Dermatomiosite/genética , Humanos
16.
Medicine (Baltimore) ; 100(9): e24372, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655912

RESUMO

RATIONALE: Severe refractory idiopathic inflammatory myopathy (IIM) represents a challenge for the clinician. The lack of efficacy of available tools reflects our incomplete insight into the molecular events sustaining the inflammatory tissue damage in these patients. We present the first case of refractory IIM treated with anti-dipeptidyl peptidase-4 (DPP-4)/cluster of differentiation 26 (CD26) monoclonal antibody. PATIENT CONCERNS: A 55-year old man presented with proximal muscle weakness, diffuse erythematous skin lesions which rapidly evolved into ulcerations, dysphagia and dysphonia. DIAGNOSIS: Increased serum creatine kinase levels and histological findings at muscle and skin biopsies were compatible with the diagnosis of dermatomyositis (DM). Several lines of treatment failed to control the disease including steroids, mycophenolate mofetil, tacrolimus, intravenous immunoglobulins and rituximab. Despite therapy, the patient also had recurrent intestinal vasculitis causing bowel perforation. Concurrently, DPP-4/CD26 expression in the patient's skin and skeletal muscle was observed. INTERVENTIONS: The patient was treated with begelomab, a murine immunoglobulin G2b monoclonal antibody against DPP-4/CD26. OUTCOMES: Dysphagia, skin lesions and intestinal vasculitis resolved and the patient experienced a significant improvement of his quality of life. CONCLUSION: Blockade of DPP-4/CD26, which is expressed on T cells and mediates T cell activation and function, is safe and might be effective in patients with refractory DM.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Dermatomiosite/tratamento farmacológico , Dipeptidil Peptidase 4/imunologia , Inibidores da Dipeptidil Peptidase IV/imunologia , Imunoglobulina G/imunologia , Dermatomiosite/imunologia , Humanos , Masculino , Pessoa de Meia-Idade
18.
Adv Rheumatol ; 61(1): 12, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608062

RESUMO

BACKGROUND: To assess the prevalence and clinical relevance of anti-Jo-1 autoantibodies in a representative sample of patients with definite dermatomyositis (DM). METHODS: This retrospective cohort study took place from 2005 to 2020 and assessed 118 adult patients from a tertiary center who were diagnosed with definite DM. A commercial kit was used to detect anti-Jo-1 autoantibodies. RESULTS: The presence of anti-Jo-1 autoantibodies was observed in 10 out of 118 (8.5%) patients with definite DM. The following variables were comparable between individuals with and without anti-Jo-1 autoantibodies: age at diagnosis, sex, ethnicity, disease duration, follow-up period, recurrence rate, complete clinical response, death rate, and cancer incidence. There was no difference in clinical features between groups, except for an increased prevalence of "mechanic's hands," joint involvement, and lung disease, as well as a reduced occurrence of skin findings in patients positive for anti-Jo-1 autoantibodies. No anti-Jo-1-positive patients went into remission; they required greater use of glucocorticoids and immunosuppressive drugs. CONCLUSIONS: Anti-Jo-1 positivity was found in 8.5% of patients with definite DM. This autoantibody was associated with an antisynthetase syndrome phenotype and might predict clinical outcomes in patients with definite DM.


Assuntos
Anticorpos Antinucleares/imunologia , Autoanticorpos/análise , Dermatomiosite/imunologia , Adulto , Fatores Etários , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Dermatomiosite/etnologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , Prednisona/uso terapêutico , Recidiva , Estudos Retrospectivos , Fatores Sexuais
19.
Ann Clin Transl Neurol ; 8(3): 677-686, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33576578

RESUMO

OBJECTIVE: This study aimed to investigate mitochondrial changes and the mitochondrial antiviral-signaling protein (MAVS)-type I interferon (IFN1) signaling pathway in the muscles of anti-melanoma differentiation gene 5(MDA5) dermatomyositis (DM) patients. METHODS: Eleven anti-MDA5 DM and ten antibody-negative DM patients were included. Muscle biopsies were performed in all patients. Muscle pathology and mitochondrial morphology in particular were compared between two groups. The expression of MDA5, MAVS, interferon (IFN) regulatory factor 7, and IFN-stimulated gene 15, which are components of the MAVS-IFN1 signaling pathway, was measured in muscle specimen. The correlation between MAVS expression in muscles and disease phenotypes and muscle pathology were analyzed. RESULTS: Anti-MDA5 DM showed a significantly lower incidence of the characteristic DM pathology (P < 0.05) than antibody-negative DM, including perifascicular fiber atrophy, inflammation, and vasculopathy. Mitochondrial abnormalities in anti-MDA5 patients revealed a high incidence of (8/11,72.7%) and different pattern from that in antibody-negative DM. MDA5, MAVS, IFN regulatory factor 7, and IFN stimulated gene 15 expression levels in the muscles of anti-MDA5 DM patients were higher than those of the controls (P < 0.05) but lower than those of antibody-negative DM patients (P < 0.05). The MAVS levels negatively correlated with manual muscle test 8 scores (r = 0.701, P = 0.016). CONCLUSIONS: Compared to antibody-negative DM, we presented a different distribution of the mitochondrial pathology and less severe morphology in anti-MDA5 DM. We also revealed the enhanced but less intensive MAVS-IFN1 signaling pathway activity in muscles of anti-MDA5 DM. Such disparity suggested the potentially different mechanism of muscle injury in two DM groups.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Dermatomiosite , Interferon Tipo I/metabolismo , Helicase IFIH1 Induzida por Interferon/imunologia , Mitocôndrias/patologia , Músculo Esquelético/metabolismo , Adulto , Idoso , Dermatomiosite/imunologia , Dermatomiosite/metabolismo , Dermatomiosite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transdução de Sinais/fisiologia
20.
BMC Pulm Med ; 21(1): 57, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579248

RESUMO

BACKGROUND: Anti-synthetase syndrome (ASSD) is a chronic autoimmune condition characterized by antibodies directed against an aminoacycl transfer RNA synthetase (ARS) along with a group of clinical features including the classical clinical triad: inflammatory myopathy, arthritis, and interstitial lung disease (ILD). ASSD is highly heterogenous due to different organ involvement, and ILD is the main cause of mortality and function loss, which presents as different patterns when diagnosed. We designed this retrospective cohort to describe the clinical features and disease behaviour of ASSD associated ILD. METHODS: Data of 108 cases of ASSD associated ILD were retrospectively collected in Beijing Chaoyang Hospital from December 2017 to March 2019. Data were obtained from the Electronic Medical Record system. Patients were divided into 5 groups according to distinct aminoacyl tRNA synthetase (ARS) antibodies. RESULTS: Overall, 108 consecutive patients were recruited. 33 were JO-1 positive, 30 were PL-7 positive, 23 were EJ positive, 13 were PL-12 positive and 9 were OJ positive. The JO-1 (+) group had a significant higher rate of mechanic's hand (57.6%) than other 4 groups. Polymyositis/dermatomyositis (PM/DM) was diagnosed in 25 (23.1%) patients and no difference was observed among the 5 groups. The PL-7 (+) group had a higher frequency of UIP pattern (13.3%) than the other 4 groups but the difference was not significant, and the EJ (+) group had the most frequent OP pattern (78.2%), which was significantly higher than the PL-7 (+) (P < 0.001) and PL-12 (+) groups (P = 0.025). The median follow-up time was 10.7 months, during which no patients died. All received prednisone treatment, with or without immunosuppressants. At the 6-month follow-up, 96.3% of all patients (104/108) had a positive response to therapy, the JO-1 (+) and EJ (+) groups had a significantly higher improvement of forced vital capacity than the other 3 groups (P < 0.05), and the PL-7 group had the lowest FVC improvement (P < 0.05). The JO-1 (+) group and EJ (+) group had significantly higher anti-Ro-52 positive occurrence than the other 3 groups (P < 0.05). CONCLUSION: Anti PL-7 antibody had the same frequency as anti-JO-1 in ASSD-ILD, in which the ILD pattern was different with distinct anti-ARS antibodies. Most ASSD-ILD had a positive response to steroid therapies, with or without immunosuppressants. The PL-7 (+) group had the highest occurrence of UIP pattern, and a significantly lower response to therapy.


Assuntos
Autoanticorpos/imunologia , Dermatomiosite/fisiopatologia , Doenças Pulmonares Intersticiais/fisiopatologia , Miosite/fisiopatologia , Adulto , Idoso , Alanina-tRNA Ligase/imunologia , Anticorpos Antinucleares/imunologia , China , Estudos de Coortes , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Feminino , Glucocorticoides/uso terapêutico , Glicina-tRNA Ligase/imunologia , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/fisiopatologia , Imunossupressores/uso terapêutico , Isoleucina-tRNA Ligase/imunologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Miosite/imunologia , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Treonina-tRNA Ligase/imunologia , Resultado do Tratamento , Capacidade Vital
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