Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 79
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-31728542

RESUMO

OBJECTIVES: To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. METHODS: Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren's syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. RESULTS: IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. CONCLUSION: We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

2.
Pathol Oncol Res ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646426

RESUMO

Association between cancer and myositis has been extensively reported and malignancy is a potentially life-threating complication in myositis. In this retrospective study authors give an overview of Hungarian cancer-associated myositis (CAM) patients treated at a single centre managing 450 myositis patients. All patients were diagnosed according to Bohan and Peter. Statistical analysis of disease onset, age, sex, muscle, skin and extramuscular symptoms, muscle enzymes, presence of antibodies, treatment and prognosis was performed. 43 patients could be considered as having CAM. 83.72% had cancer within one year of diagnosis of myositis. Most common localizations were ductal carcinoma of breast and adenocarcinoma of lung. Significant differences were observed between CAM and the non-CAM control patients: DM:PM ratio was 2.31:1 vs. 0.87:1, respectively (p = 0.029), age at diagnosis was 56.60 ± 12.79 vs. 38.88 ± 10.88 years, respectively (p < 0.001). Tumour-treatment was the following: surgical removal in 55.81%, chemotherapy in 51.1%, radiotherapy in 39.53%, hormone treatment in 18.6%, combination therapy in 51.16% of patients. Muscle enzyme levels of patients undergoing surgery were significantly reduced after intervention. 36 patients died (83.72%); 25 DM (83.33%) and 11 PM patients (84.62%); 5 years survival was 15.4% for PM and 27.5% for DM. This study demonstrates that DM, distal muscle weakness, asymmetric Raynaud's phenomenon, older age, ANA-negativity are risk factors for developing malignancy and polymyositis patients have less chance of long-lasting survival. It is very important to think about cancer and follow every single myositis patient in the clinical routine because survival rate of CAM is very poor.

3.
Ann Rheum Dis ; 78(7): 996-1002, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31138531

RESUMO

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10-5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10-53 and HLA-DRB1*03:01, p=3.25×10-9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10-26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10-11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10-13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10-6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10-64) and position 9 of HLA-B (p=7.03×10-11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.

4.
Biomed Res Int ; 2018: 6416378, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498759

RESUMO

The aim of this study was to determine the clinical, serological, and genetic features of anti-Jo-1 positive antisynthetase patients followed by a Hungarian single centre to identify prognostic markers, which can predict disease phenotypes and disease progression. It was a retrospective study using clinical database of 49 anti-Jo-1 positive patients. 100% of patients exhibited myositis, 73% interstitial lung disease, 88% arthritis, 65% Raynaud's phenomenon, 43% fever, 33% mechanic's hand, and 12% dysphagia. We could detect significant correlation between anti-Jo-1 titer and the CK and CRP levels at disease onset and during disease course. HLA DRB1⁎03 positivity was present in 68.96% of patients, where the CK level at diagnosis was significantly lower compared to the HLA DRB1⁎03 negative patients. HLA DQA1⁎0501-DQB1⁎0201 haplotype was found in 58.62% of patients, but no significant correlation was found regarding any clinical or laboratory features. Higher CRP, ESR level, RF positivity, and the presence of fever or vasculitic skin lesions at the time of diagnosis indicated a higher steroid demand and the administration of higher number of immunosuppressants during the follow-up within anti-Jo-1 positive patients. The organ involvement of the disease was not different in HLA-DRB1⁎0301 positive or negative patients who were positive to the anti-Jo-1 antibody; however, initial CK level was lower in HLA-DRB1⁎0301 positive patients. Distinct laboratory and clinical parameters at diagnosis could be considered as prognostic markers.

5.
Ocul Immunol Inflamm ; : 1-9, 2018 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-30444429

RESUMO

PURPOSE: To evaluate corneal parameters in patients with polymyositis (PM) and dermatomyositis (DM) and compare them with those of healthy controls. METHODS: A total of 43 PM and 32 DM patients and 93 controls were enrolled in this cross-sectional, observational, case-control study. Corneal parameters were evaluated by Pentacam. Objective clinical tests of dry eye disease (DED) were also performed. RESULTS: All pachymetric measurements and corneal volumes (CVs) proved to be significantly lower both in PM and DM patients. The values of DM patients were closer to control values than those of the PM patients. For tear break-up time and Schirmer-I test values significant differences were observed between patients and controls, with values decreased both in PM and DM patients. CONCLUSIONS: PM patients rather than DM patients tend to develop thinner and low-volume corneas as compared to controls. Additionally, a high prevalence of DED among both PM and DM patients was also detected.

7.
Ann Rheum Dis ; 77(1): 30-39, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28855174

RESUMO

AIMS: The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. METHODS: Cross-sectional analysis of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated. RESULTS: Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001).Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001).ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases ('V' sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%. CONCLUSION: This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients.


Assuntos
Pesquisa Biomédica/métodos , Cooperação Internacional , Miosite/epidemiologia , Sistema de Registros/estatística & dados numéricos , Estudos de Coortes , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Miosite/etiologia , Miosite/patologia , Prognóstico , Índice de Gravidade de Doença , Fumar/efeitos adversos , Inquéritos e Questionários
8.
RMD Open ; 3(2): e000507, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29177080

RESUMO

Objective: To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups. Methods: An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach. Results: The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria. Conclusions: The new EULAR/ACR classification criteria provide a patient's probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.

9.
Arthritis Rheumatol ; 69(12): 2271-2282, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29106061

RESUMO

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM." CONCLUSION: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.


Assuntos
Miosite/classificação , Miosite/diagnóstico , Guias de Prática Clínica como Assunto , Reumatologia/normas , Avaliação de Sintomas/normas , Adolescente , Adulto , Biópsia/normas , Criança , Consenso , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Sensibilidade e Especificidade , Sociedades Médicas , Avaliação de Sintomas/métodos , Estados Unidos , Adulto Jovem
11.
Ann Rheum Dis ; 76(12): 1955-1964, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29079590

RESUMO

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. CONCLUSIONS: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.


Assuntos
Miosite/classificação , Miosite/diagnóstico , Reumatologia/normas , Adulto , Biópsia/normas , Criança , Consenso , Diagnóstico Diferencial , Europa (Continente) , Humanos , Músculo Esquelético/patologia , Probabilidade , Valores de Referência , Reumatologia/organização & administração , Sensibilidade e Especificidade , Sociedades Médicas/organização & administração , Estados Unidos
12.
Rheumatology (Oxford) ; 56(11): 1884-1893, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28977549

RESUMO

Objective: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results: Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion: Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.


Assuntos
Dermatomiosite/terapia , Área Sob a Curva , Humanos , Modelos Logísticos , Diferença Mínima Clinicamente Importante , Polimiosite/terapia , Resultado do Tratamento
13.
Orv Hetil ; 158(35): 1382-1389, 2017 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-28847176

RESUMO

INTRODUCTION: Idiopathic inflammatory myopathies are a group of clinically heterogeneous diseases, which have been classified by myositis specific antibodies recently. The anti-SRP positive subset of this group is characterized by more severe clinical prognosis than other myositis specific antibody positive types. AIM: Our goal was to compare 16 anti-SRP positive patients in the Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen with 16 antibody negative ones. METHOD: Muscle strength validated in both groups by the manual muscle test proved to be significantly decreased both before and after therapy (χ2 = 0.006 and 0.019) in the anti-SRP positive group. RESULTS: Muscle-specific inflammatory laboratory parameters showed significant difference only in case of LDH-levels after therapy. Both groups showed good clinical response to first line steroid treatment, yet the significantly higher rate of second line administration suggests worse therapeutic response of the antibody positive group. CONCLUSION: Based on these facts we determined poor clinical prognosis and therapeutic response of the anti-SRP positive group. Orv Hetil. 2017; 158(35): 1382-1389.


Assuntos
Autoanticorpos/imunologia , Músculo Esquelético/imunologia , Miosite/imunologia , Partícula de Reconhecimento de Sinal/imunologia , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Miosite/tratamento farmacológico , Miosite/patologia , Prognóstico
14.
Expert Rev Clin Pharmacol ; 10(10): 1109-1118, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28691537

RESUMO

INTRODUCTION: Dermatomyositis is a rare heterogeneous systemic autoimmune disease with multiple organ involvement which can result in significant disability and mortality. Despite the lack of placebo-controlled trials, glucocorticoids are considered to be the mainstay of initial management. Treatment strategies are mainly based on uncontrolled studies, evidence based guidelines for treatments do not exist. Areas covered: This review provides an overview of the currently available pharmacological treatments in the field of dermatomyositis including conventional immunosuppressants, biologics and topical agents. The role of antibodies in different treatment responses of dermatomyositis related clinicoserological syndromes is also discussed. A PubMed search was performed in order to find relevant literature for this review. Expert commentary: Early recognition and intervention is essential to ameliorate disease outcome. Determination of antibodies provide a useful key in diagnosis, clinical manifestations, malignancy, prognosis, and treatment response and may lead to wider acceptance of personalized medicine. Corticosteroids with adjunctive steroid-sparing immunosuppressive therapies are recommended to treat disease activity, prevent mortality, and reduce long-term disability. Combinations of second-line therapies or newer third-line therapies are used in severe, refractory, or corticosteroid-dependent diseases. Further research is required to assess the role of new therapies.


Assuntos
Anticorpos/imunologia , Dermatomiosite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Administração Cutânea , Produtos Biológicos/administração & dosagem , Produtos Biológicos/uso terapêutico , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Medicina de Precisão , Prognóstico
15.
Ann Rheum Dis ; 76(5): 792-801, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28385805

RESUMO

To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.


Assuntos
Dermatomiosite/terapia , Avaliação de Resultados (Cuidados de Saúde)/normas , Índice de Gravidade de Doença , Adolescente , Adulto , Criança , Pré-Escolar , Consenso , Humanos , Polimiosite/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade
16.
Arthritis Rheumatol ; 69(5): 898-910, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28382787

RESUMO

OBJECTIVE: To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). METHODS: Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. RESULTS: Consensus was reached for a conjoint analysis-based continuous model using absolute percent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (P < 0.001). CONCLUSION: The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute percent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.


Assuntos
Antirreumáticos/uso terapêutico , Dermatomiosite/tratamento farmacológico , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Creatina Quinase/metabolismo , Dermatomiosite/metabolismo , Dermatomiosite/fisiopatologia , Europa (Continente) , Frutose-Bifosfato Aldolase/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Modelos Logísticos , Força Muscular , Avaliação de Resultados (Cuidados de Saúde) , Medidas de Resultados Relatados pelo Paciente , Polimiosite/tratamento farmacológico , Polimiosite/metabolismo , Polimiosite/fisiopatologia , Reumatologia , Sociedades Médicas , Inquéritos e Questionários , Resultado do Tratamento , Estados Unidos
17.
Arthritis Rheumatol ; 69(5): 1090-1099, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28086002

RESUMO

OBJECTIVE: Inclusion body myositis (IBM) is characterized by a combination of inflammatory and degenerative changes affecting muscle. While the primary cause of IBM is unknown, genetic factors may influence disease susceptibility. To determine genetic factors contributing to the etiology of IBM, we conducted the largest genetic association study of the disease to date, investigating immune-related genes using the Immunochip. METHODS: A total of 252 Caucasian patients with IBM were recruited from 11 countries through the Myositis Genetics Consortium and compared with 1,008 ethnically matched controls. Classic HLA alleles and amino acids were imputed using SNP2HLA. RESULTS: The HLA region was confirmed as the most strongly associated region in IBM (P = 3.58 × 10-33 ). HLA imputation identified 3 independent associations (with HLA-DRB1*03:01, DRB1*01:01, and DRB1*13:01), although the strongest association was with amino acid positions 26 and 11 of the HLA-DRB1 molecule. No association with anti-cytosolic 5'-nucleotidase 1A-positive status was found independent of HLA-DRB1*03:01. There was no association of HLA genotypes with age at onset of IBM. Three non-HLA regions reached suggestive significance, including the chromosome 3 p21.31 region, an established risk locus for autoimmune disease, where a frameshift mutation in CCR5 is thought to be the causal variant. CONCLUSION: This is the largest, most comprehensive genetic association study to date in IBM. The data confirm that HLA is the most strongly associated region and identifies novel amino acid associations that may explain the risk in this locus. These amino acid associations differentiate IBM from polymyositis and dermatomyositis and may determine properties of the peptide-binding groove, allowing it to preferentially bind autoantigenic peptides. A novel suggestive association within the chromosome 3 p21.31 region suggests a role for CCR5.


Assuntos
Cadeias HLA-DRB1/genética , Miosite de Corpos de Inclusão/genética , Idade de Início , Autoanticorpos/imunologia , Cromossomos Humanos Par 3/genética , Grupo com Ancestrais do Continente Europeu/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Miosite de Corpos de Inclusão/imunologia , Receptores CCR5/genética
18.
Autoimmun Rev ; 15(10): 983-93, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27491568

RESUMO

In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria.


Assuntos
Autoanticorpos/metabolismo , Doenças Autoimunes/induzido quimicamente , Hidroximetilglutaril-CoA Redutases/imunologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/imunologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Biomarcadores/metabolismo , Humanos , Estudos Multicêntricos como Assunto , Doenças Musculares/induzido quimicamente , Doenças Musculares/metabolismo , Necrose/induzido quimicamente , Necrose/imunologia , Curva ROC
19.
Orv Hetil ; 157(30): 1179-84, 2016 Jul.
Artigo em Húngaro | MEDLINE | ID: mdl-27452067

RESUMO

Myositis, which means inflammation of the muscles, is a general term used for inflammatory myopathies. Myositis is a rare idiopathic autoimmune disease. It is believed that environmental factors such as virus, bacteria, parasites, direct injuries, drugs side effect can trigger the immune system of genetically susceptible individuals to act against muscle tissues. There are several types of myositis with the same systemic symptoms such as muscle weakness, fatigue, muscle pain and inflammation. These include dermatomyositis, juvenile dermatomyositis, inclusion-body myositis, polymyositis, orbital myositis and myositis ossificans. Juvenile and adult dermatomyositis are chronic, immune-mediated inflammatory myopathies characterized by progressive proximal muscle weakness and typical skin symptoms. The aim of the authors was to compare the symptoms, laboratory and serological findings and disease course in children and adult patients with idiopathic inflammatory myopathy. Early diagnosis and aggressive immunosuppressive treatment improve the mortality of these patients. Myositis-specific autoantibodies have predictive and prognostic values regarding the associated overlap disease, response to treatment and disease course. The authors intend to lighten the clinical and pathogenetic significance of the new target autoantigens. Orv. Hetil., 2016, 157(29), 1179-1184.


Assuntos
Autoanticorpos/sangue , Autoantígenos/efeitos dos fármacos , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Imunossupressores/uso terapêutico , Miosite/diagnóstico , Miosite/imunologia , Adolescente , Adulto , Criança , Doença Crônica , Dermatomiosite/diagnóstico , Dermatomiosite/imunologia , Progressão da Doença , Diagnóstico Precoce , Fadiga/imunologia , Humanos , Imunossupressores/administração & dosagem , Debilidade Muscular/imunologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/imunologia , Miosite Orbital/diagnóstico , Miosite Orbital/imunologia , Polimiosite/diagnóstico , Polimiosite/imunologia , Valor Preditivo dos Testes , Prognóstico
20.
Orv Hetil ; 157(15): 575-83, 2016 Apr 10.
Artigo em Húngaro | MEDLINE | ID: mdl-27039996

RESUMO

INTRODUCTION: In idiopathic inflammatory myopathies, the presence of anti-Jo-1 antibody defines a distinct clinical phenotype (myositis, arthritis, interstitial lung disease, Raynaud's phenomenon fever, mechanic's hands), called antisynthetase syndrome. AIM: To determine the demographic data as well as clinical, laboratory and terapeutical features of anti-Jo1 positive patients, followed by the department of the authors. METHOD: The medical records of 49 consecutive anti-Jo1 patients were reviewed. RESULTS: Demographic and clinical results were very similar to those published by other centers. Significant correlation was found between the anti-Jo-1 titer and the creatine kinase and C-reactive protein levels. Distinct laboratory results measured at the time of diagnosis of the disease (C-reactive protein, antigen A associated with Sjogren's syndrome, positive rheumatoid factor), and the presence of certain clinical symptoms (fever, vasculitic skin) may indicate a worse prognosis within the antisyntetase positive patient group. CONCLUSION: In the cases above more agressive immunosuppressive therapy may be required.


Assuntos
Anticorpos Antinucleares/imunologia , Autoanticorpos/sangue , Imunossupressores/uso terapêutico , Miosite/imunologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite/imunologia , Proteína C-Reativa/metabolismo , Creatina Quinase/sangue , Dermatomiosite/imunologia , Feminino , Febre/imunologia , Humanos , Hungria , Imunoglobulinas Intravenosas/uso terapêutico , Doenças Pulmonares Intersticiais/imunologia , Masculino , Registros Médicos , Pessoa de Meia-Idade , Miosite/tratamento farmacológico , Miosite/patologia , Miosite/fisiopatologia , Polimiosite/imunologia , Doença de Raynaud/imunologia , Estudos Retrospectivos , Rituximab/uso terapêutico , Índice de Gravidade de Doença , Síndrome de Sjogren/imunologia , Vasculite/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA