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1.
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
2.
BMC Pulm Med ; 21(1): 11, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407281

RESUMO

BACKGROUND: Anti-synthetase syndrome (ASS) is an uncommon immune-mediated entity characterized by myositis, interstitial lung disease (ILD), non-erosive arthritis, and less common features such as fever, Raynaud's phenomenon, and skin changes in association with anti-aminoacyl-transfer-RNA antibodies, most commonly anti-Jo-1 antibodies. CASE PRESENTATION: We present a challenging and rare case of ASS-associated ILD presenting with unexplained respiratory symptoms and bilateral infiltrates on chest imaging during the COVID-19 pandemic. High clinical suspicion for ASS with early appropriate therapy with corticosteroids and immunosuppressive agents led to marked clinical improvement. CONCLUSION: High index of suspicion for ASS is mandated in patients with unexplained ILD. A comprehensive autoimmune work-up is important as an early treatment with corticosteroids with or without immunomodulators improves patient outcomes and survival in an otherwise poor prognostic disease.


Assuntos
Autoanticorpos/imunologia , Pulmão/diagnóstico por imagem , Miosite/diagnóstico , Pandemias , Doenças Raras , Comorbidade , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Miosite/epidemiologia , Miosite/imunologia , Prognóstico
3.
Med. clín (Ed. impr.) ; 155(12): 541-547, dic. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-198358

RESUMO

In recent years, immunotherapy has become an important pillar of cancer treatment, with high response rates regardless of tumour histology or baseline mutations. However, immune activation associated with check-point inhibitors is not selective and a large variety of immune-related adverse events have been associated with anti-PD1, anti-PD-1/L-1 and anti-CTLA-4 agents. Though diagnosis and treatment of these toxicities have been established according to the recommendations from clinical trials and in line with the autoimmune disorders that they mimic, increasing real-world data is coming up showing that these adverse events may have differential characteristics and management, especially in terms of the use of corticoids, second-line treatments, salvage therapy for life-threatening cases and reintroduction of immunotherapy. Herein we present a comprehensive review of current recommendations and real-world data on the main immune-related adverse events of immunotherapy


En los últimos años la inmunoterapia se ha convertido en un pilar fundamental para el tratamiento del cáncer, con altas tasas de respuesta, independientemente de la histología tumoral o de las mutaciones basales. Sin embargo, la activación inmune asociada a los inhibidores de control no es selectiva, habiéndose asociado una gran variedad de efectos adversos relacionados con la inmunidad a los agentes anti-PD1, anti-PD-1/L-1 y anti-CTLA-4. Aunque se han establecido el diagnóstico y el tratamiento de estas toxicidades en virtud de las recomendaciones de los ensayos clínicos, en consonancia con los trastornos autoinmunes que imitan, el incremento de los datos del mundo real refleja que dichos efectos adversos pueden tener características y manejos diferenciales, especialmente en términos de uso de corticoides, tratamientos de segunda línea, terapia de rescate para casos potencialmente letales, y reintroducción de la inmunoterapia. Presentamos aquí una revisión amplia de las recomendaciones actuales y los datos del mundo real sobre los principales efectos adversos de la inmunoterapia


Assuntos
Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias/imunologia , Neoplasias/terapia , Ensaios Clínicos como Assunto , Imunoterapia/efeitos adversos , Hepatite/imunologia , Hepatite/terapia , Miosite/imunologia , Miosite/terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
4.
Neurol Clin ; 38(3): 661-678, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32703475

RESUMO

Inflammatory myopathies are a group of immune-mediated muscle disorders comprising dermatomyositis; polymyositis; overlap myositis, including antisynthetase syndromes and nonspecific myositis, immune-mediated necrotizing myopathies, and sporadic inclusion body myositis. They are now much more eloquently classified both pathologically and clinically because of the discovery of several myositis-specific and myositis-associated antibodies. These antibodies also aid in choosing the best treatment options in each case. Based on the initial classifications of inflammatory myopathies, inclusion body myositis, overlap myositis, and necrotizing myositis were all included in the polymyositis group. This article discusses cases, diagnostic tools, associated antibodies, and pathology.


Assuntos
Autoanticorpos/sangue , Miosite/sangue , Miosite/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Feminino , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Miosite/imunologia , Miosite de Corpos de Inclusão/sangue , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/imunologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-32518172

RESUMO

OBJECTIVE: To present the COVID-19-associated GBS, the prototypic viral-triggered autoimmune disease, in the context of other emerging COVID-19-triggered autoimmunities, and discuss potential concerns with ongoing neuroimmunotherapies. METHODS: Eleven GBS cases in four key COVID-19 hotspots are discussed regarding presenting symptoms, response to therapies and cross-reactivity of COVID spike proteins with nerve glycolipids. Emerging cases of COVID-19-triggered autoimmune necrotizing myositis (NAM) and encephalopathies are also reviewed in the context of viral invasion, autoimmunity and ongoing immunotherapies. RESULTS: Collective data indicate that in this pandemic any patient presenting with an acute paralytic disease-like GBS, encephalomyelitis or myositis-even without systemic symptoms, may represent the first manifestation of COVID-19. Anosmia, ageusia, other cranial neuropathies and lymphocytopenia are red flags enhancing early diagnostic suspicion. In Miller-Fisher Syndrome, ganglioside antibodies against GD1b, instead of QG1b, were found; because the COVID-19 spike protein also binds to sialic acid-containing glycoproteins for cell-entry and anti-GD1b antibodies typically cause ataxic neuropathy, cross-reactivity between COVID-19-bearing gangliosides and peripheral nerve glycolipids was addressed. Elevated Creatine Kinase (>10,000) is reported in 10% of COVID-19-infected patients; two such patients presented with painful muscle weakness responding to IVIg indicating that COVID-19-triggered NAM is an overlooked entity. Cases of acute necrotizing brainstem encephalitis, cranial neuropathies with leptomeningeal enhancement, and tumefactive postgadolinium-enhanced demyelinating lesions are now emerging with the need to explore neuroinvasion and autoimmunity. Concerns for modifications-if any-of chronic immunotherapies with steroids, mycophenolate, azathioprine, IVIg, and anti-B-cell agents were addressed; the role of complement in innate immunity to viral responses and anti-complement therapeutics (i.e. eculizumab) were reviewed. CONCLUSIONS: Emerging data indicate that COVID-19 can trigger not only GBS but other autoimmune neurological diseases necessitating vigilance for early diagnosis and therapy initiation. Although COVID-19 infection, like most other viruses, can potentially worsen patients with pre-existing autoimmunity, there is no evidence that patients with autoimmune neurological diseases stable on common immunotherapies are facing increased risks of infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Miosite/diagnóstico , Miosite/etiologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/etiologia , Doenças Autoimunes do Sistema Nervoso/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Feminino , Síndrome de Guillain-Barré/imunologia , Humanos , Masculino , Miosite/imunologia , Pandemias , Pneumonia Viral/imunologia
6.
J Neuropathol Exp Neurol ; 79(4): 448-457, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32100014

RESUMO

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and antisignal recognition particle (SRP) antibodies are frequently associated with immune-mediated necrotizing myopathy (IMNM). However, the difference in clinical manifestations between anti-HMGCR and anti-SRP antibodies is unclear. HMGCR is an essential enzyme for cholesterol biosynthesis and is inhibited by statins that regulate apoptosis of Bcl-2-positive and beta chemokine receptor 4 (CCR4)-positive lymphoma cells. In this study, we aimed to clarify Bcl-2 and CCR4 expressions of lymphocytes in anti-HMGCR antibody-positive IMNM and explore the difference between anti-HMGCR antibody-positive myopathy and other inflammatory myopathies. We retrospectively examined Bcl-2- and CCR4-positive lymphocyte infiltrations in muscle and skin biopsy specimens from 19 anti-HMGCR antibody-positive patients and 75 other idiopathic inflammatory myopathies (IIMs) patients. A higher incidence of Bcl-2- and CCR4-positive lymphocytes was detected in the muscle and skin of anti-HMGCR antibody-positive IMNM patients (p < 0.001). In 5 patients with anti-HMGCR antibodies, Bcl-2-positive lymphocytes formed lymphocytic accumulations, which were not observed in other IIMs. Low-density lipoprotein cholesterol levels were not increased except for patients with Bcl-2-positive lymphocytic accumulations (p = 0.010). Bcl-2 and CCR4 lymphocyte infiltrations could be a pathological characteristic of anti-HMGCR antibody-positive IMNM.


Assuntos
Hidroximetilglutaril-CoA Redutases/imunologia , Linfócitos/imunologia , Doenças Musculares/imunologia , Doenças Musculares/patologia , Miosite/imunologia , Miosite/patologia , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Receptores CCR4/imunologia , Adulto , Anticorpos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Doenças Musculares/complicações , Miosite/complicações , Dermatopatias/imunologia , Dermatopatias/patologia
8.
Chest ; 157(2): e41-e45, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32033660

RESUMO

CASE PRESENTATION: A 72-year-old man presented to our ED less than 24 hours following the acute onset of nausea, vomiting, and diarrhea. Within 12 hours of symptom onset, he noted bilateral lower extremity pain and swelling. His pain was associated with a new violaceous irregular rash on the anterior aspect of both feet and legs. There was no history of inciting trauma or recent wounds. In addition, there was no history of consumption of raw or undercooked food (including seafood) or recent change in food source. There was accompanying fever and chills for the same duration and painful swelling of his left thumb. His comorbidities included stage IIIb classical Hodgkin lymphoma diagnosed 4 months prior. His last dose of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy was 4 days before presentation. He had previously failed anti-CD30 monoclonal therapy resulting from attributed pancolitis.


Assuntos
Celulite (Flegmão)/diagnóstico , Gastroenterite/diagnóstico , Doença de Hodgkin/imunologia , Hospedeiro Imunocomprometido , Miosite/diagnóstico , Sepse/diagnóstico , Vibrioses/diagnóstico , Idoso , Antibacterianos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Celulite (Flegmão)/imunologia , Celulite (Flegmão)/terapia , Desbridamento , Gastroenterite/imunologia , Gastroenterite/terapia , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Humanos , Dermatoses da Perna , Masculino , Miosite/imunologia , Miosite/terapia , Músculo Quadríceps/diagnóstico por imagem , Sepse/imunologia , Sepse/terapia , Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/imunologia , Infecções dos Tecidos Moles/terapia , Tomografia Computadorizada por Raios X , Vibrioses/imunologia , Vibrioses/terapia , Vibrio vulnificus
10.
Arthritis Res Ther ; 22(1): 5, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059

RESUMO

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.


Assuntos
Doenças Autoimunes/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imunossupressores/uso terapêutico , Miosite/induzido quimicamente , Miosite/etiologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/tratamento farmacológico , Feminino , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Quimioterapia de Indução/métodos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , Estudos Retrospectivos
14.
Arthritis Rheumatol ; 72(1): 179-191, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403245

RESUMO

OBJECTIVE: Autoantibodies targeting histidyl-transfer RNA synthetase (HisRS; anti-Jo-1) are common in the idiopathic inflammatory myopathies (IIMs) and antisynthetase syndrome. This study was undertaken to investigate immunity against HisRS in the blood and lungs of patients with IIM/antisynthetase syndrome. METHODS: Bronchoalveolar lavage (BAL) fluid, BAL fluid cells, and peripheral blood mononuclear cells (PBMCs) from patients with IIM/antisynthetase syndrome (n = 24) were stimulated with full-length HisRS protein or a HisRS-derived peptide (HisRS11-23 ). BAL fluid and PBMCs from patients with sarcoidosis (n = 7) and healthy subjects (n = 12) were included as controls. The CD4+ T cell response was determined according to levels of CD40L up-regulation and cytokine expression using flow cytometry. Anti-Jo-1 autoantibody responses in the serum and BAL fluid were assessed by enzyme-linked immunosorbent assay. Lung biopsy samples from patients with IIM/antisynthetase syndrome (n = 14) were investigated by immunohistochemistry. RESULTS: In BAL fluid, CD4+ T cells from 3 of 4 patients with IIM/antisynthetase syndrome responded to stimulation with HisRS protein, as measured by the median fold change in CD40L expresssion in stimulated cells compared to unstimulated cells (median fold change 3.6, interquartile range [IQR] 2.7-14.7), and 2 of 3 patients with IIM/antisynthetase syndrome had the highest responses to HisRS11-23 (median fold change 88, IQR 27-149). In PBMCs, CD4+ T cells from 14 of 18 patients with IIM/antisynthetase syndrome responded to HisRS protein (median fold change 7.38, IQR 2.69-31.86; P < 0.001), whereas a HisRS11-23 response was present in 11 of 14 patients with IIM/antisynthetase syndrome (median fold change 3.4, IQR 1.87-10.9; P < 0.001). In the control group, there was a HisRS11-23 response in 3 of 7 patients with sarcoidosis (median fold change 2.09, IQR 1.45-3.29) and in 5 of 12 healthy controls (median fold change 2, IQR 1.89-2.42). CD4+ T cells from patients with IIM/antisynthetase syndrome displayed a pronounced Th1 phenotype in the BAL fluid when compared to the PBMCs (P < 0.001), producing high amounts of interferon-γ and interleukin-2 following stimulation. Anti-Jo-1 autoantibodies were detected in BAL fluid and germinal center (GC)-like structures were seen in the lung biopsy samples from patients with IIM/antisynthetase syndrome. CONCLUSION: The results of this study demonstrate a pronounced presence of HisRS-reactive CD4+ T cells in PBMCs and BAL fluid cells from patients with IIM/antisynthetase syndrome as compared to patients with sarcoidosis and healthy controls. These findings, combined with the presence of anti-Jo-1 autoantibodies in BAL fluid and GC-like structures in the lungs, suggest that immune activation against HisRS might take place within the lungs of patients with IIM/antisynthetase syndrome.


Assuntos
Anticorpos Antinucleares/imunologia , Linfócitos T CD4-Positivos/imunologia , Doenças Pulmonares Intersticiais/imunologia , Pulmão/imunologia , Monócitos/imunologia , Miosite/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Feminino , Histidina-tRNA Ligase/imunologia , Humanos , Interferon gama/imunologia , Interleucina-2/imunologia , Pulmão/citologia , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Células Th1
16.
Clin Exp Rheumatol ; 38(1): 67-73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31365334

RESUMO

OBJECTIVES: To investigate anti-TIF1-γ antibodies in longitudinally followed patients with myositis and cancer. METHODS: Serum levels of anti-TIF1-γ antibodies at different time-points in relation to myositis and cancer diagnosis were analysed by ELISA in 79 patients from a Swedish cohort with polymyositis (PM) and dermatomyositis (DM) and a Spanish cohort restricted to DM patients. Anti-TIF1-γ positive and negative patients were compared with Fisher's exact test, student t-tests and Wilcoxon test. RESULTS: Thirty-six patients (17 from cohort 1 and 19 from cohort 2) with myositis and cancer were anti-TIF1-γ antibody positive; all had DM. In 88% of anti-TIF1-γ positive patients, cancer was diagnosed within 3 years from DM diagnosis compared to 63% in anti-TIF1-γ negative. Four DM patients, anti-TIF1-γ positive at cancer diagnosis had positive serum samples even antedating cancer diagnosis up to five years. In cohort 1 the median (interquartile range) antibody level was higher, 2.13 au (1.82-2.15), in the seven patients who died <1 year after cancer diagnosis, compared to the seven that died >1 year after cancer diagnosis, 1.34 au (0.92-1.59), (p=0.004). Three patients were still alive and in remission from cancer and DM 14-16 years after cancer treatment of whom two became negative for anti-TIF1-γ antibodies. In the second cohort remission of cancer coincided with remission of DM and low or negative serum levels of autoantibodies. CONCLUSIONS: Anti-TIF1-γ antibodies may be detected before clinical symptoms of cancer and may disappear after successful treatment of cancer with remission of DM supporting DM being a paramalignant phenomenon.


Assuntos
Autoanticorpos , Dermatomiosite , Miosite , Neoplasias , Proteínas Nucleares , Polimiosite , Fatores de Transcrição , Humanos , Estudos Longitudinais , Miosite/complicações , Miosite/imunologia , Miosite/terapia , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/terapia , Proteínas Nucleares/imunologia , Fatores de Transcrição/imunologia
18.
Clin Exp Rheumatol ; 38(2): 212-219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31287411

RESUMO

OBJECTIVES: Today, the contribution of myositis-specific autoantibodies (MSA) in the diagnostic workup of idiopathic inflammatory myopathies (IIM) is on the rise. The aim of this study was to document MSA frequency as detected by lineblot in a set of consecutive MSA requests and to correlate the results with clinical diagnosis, IIM subtype and indirect immunofluorescence (IIF) findings. Additionally, a comparison between two lineblots was performed. METHODS: A total of 118 consecutive samples of patients with suspicion of IIM were analysed on IIF and two lineblots. A total of 107 patients with autoimmune rheumatic diseases served as controls. RESULTS: MSA were detected in 55% of IIM patients (n=31) and 7.9% (n=12) of patients without clinical diagnosis of IIM or myositis overlap syndrome. All the IIM patients had a MSA-compatible clinical subtype. There was no to fair agreement between both lineblots for the individual antibodies, with most discrepancies observed for anti-TIF1γ (κ=-0.021), anti-SRP (κ=-0.006) and anti-SAE (κ=0.395). Differences between both assays were mostly observed in the non-IIM patients, also showing signi cantly lower blot signal intensities compared to IIM patients (p=0.0013). MSA in the non-IIM patients frequently showed an incompatible IIF pattern. CONCLUSIONS: Lineblot seems to be an interesting tool for MSA detection in a clinical context, allowing the identification of clinical subtypes. However, considerable caution must be exercised in interpreting the results in case of low positive MSA signal intensity, discordant lineblot results and/or an incompatible IIF pattern.


Assuntos
Autoanticorpos/imunologia , Miosite/diagnóstico , Miosite/imunologia , Autoanticorpos/sangue , Doenças Autoimunes , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Síndrome
19.
Rheumatology (Oxford) ; 59(1): 194-204, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292651

RESUMO

OBJECTIVE: The inflammatory idiopathic myopathies (IIM) are a group of rare autoimmune diseases defined by muscle weakness and characterized by pro-inflammatory infiltrates in muscle. Little is known about the immunological profile in peripheral blood of these patients and how this relates to IIM subtypes. This study aimed to stratify adult and juvenile-onset IIM patients according to immune cell profile. METHODS: Peripheral blood mononuclear cells from 44 patients with adult myositis (AM), 15 adolescent-onset juvenile dermatomyositis (a-JDM), and 40 age-matched healthy controls were analysed by flow cytometry to quantify 33 immune cell subsets. Adult myositis patients were grouped according to myositis subtype; DM and polymyositis; and also autoantibody specificity. Disease activity was determined by the myositis disease activity assessment tool and clinicians' decision on treatment. RESULTS: Unique immune signatures were identified for DM, polymyositis and a-JDM compared with healthy controls. DM patients had a T-cell signature comprising increased CD4+ and TH17 cell frequencies and increased immune cell expression of IL-6. Polymyositis patients had a B-cell signature with reduced memory B cells. A-JDM had decreased naïve B cells and increased CD4+T cells. All patient groups had decreased CD8+central memory T-cell frequencies. The distinct immune signatures were also seen when adult myositis patients were stratified according to auto-antibody expression; patients with anti-synthetase-antibodies had reduced memory B cells and patients with autoimmune rheumatic disease overlap had an elevated Th17 profile. CONCLUSION: Unique immune signatures were associated with adult vs juvenile disease. The Th17 signature in DM patients supports the potential use of IL-17 inhibitors in treatment of IIMs.


Assuntos
Autoanticorpos/sangue , Imunidade Celular , Leucócitos Mononucleares/imunologia , Miosite/imunologia , Adolescente , Adulto , Linfócitos B/imunologia , Biomarcadores/sangue , Feminino , Citometria de Fluxo , Humanos , Interleucina-6/sangue , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Linfócitos T/imunologia , Adulto Jovem
20.
Rheumatology (Oxford) ; 59(7): 1626-1631, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31665469

RESUMO

OBJECTIVES: It has been over 10 years since the first report of autoantibodies directed against phenylalanyl tRNA synthetase (anti-Zo) in a patient with features of the anti-synthetase syndrome. In that time no further cases have been published. Here we aim to characterize more fully the clinical phenotype of anti-Zo-associated myositis by describing the clinical features of nine patients. METHODS: Anti-Zo was identified by protein-immunoprecipitation in patients referred for extended spectrum myositis autoantibody testing at our laboratory. Results were confirmed by immunodepletion using a reference serum. Medical records were retrospectively reviewed to provide detailed information of the associated clinical phenotype for all identified patients. Where possible, HLA genotype was imputed using Illumina protocols. RESULTS: Nine patients with anti-Zo were identified. The median age at disease onset was 51 years, and six patients were female. Seven patients had evidence of inflammatory muscle disease, seven of interstitial lung disease and six of arthritis. The reported pattern of interstitial lung disease varied with usual interstitial pneumonia, non-specific interstitial pneumonia and organizing pneumonia all described. Other features of the anti-synthetase syndrome such as RP and mechanics hands were common. HLA data was available for three patients, all of whom had at least one copy of the HLA 8.1 ancestral haplotype. CONCLUSION: Patients with anti-Zo presenting with features of the anti-synthetase syndrome and interstitial lung disease is a common finding. Like other myositis autoantibodies, there is likely to be a genetic association with the HLA 8.1 ancestral haplotype.


Assuntos
Autoanticorpos/sangue , Miosite/diagnóstico , Fenilalanina-tRNA Ligase/imunologia , Adulto , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/imunologia , Fenótipo , Estudos Retrospectivos , Reino Unido
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