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2.
Commun Biol ; 4(1): 419, 2021 Mar 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.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33599244

RESUMO

OBJECTIVES: To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. METHODS: A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared to the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesised via narrative review. RESULTS: Sixty nine studies were included in the meta-analysis. Dermatomyositis subtype (RR 2.21), older age (WMD 11.19), male gender (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73), and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. Polymyositis (RR 0.49) and clinically amyopathic dermatomyositis (RR 0.44) subtypes, Raynaud's phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD -1189.96) or lactate dehydrogenase (WMD -336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. Computed tomography (CT) scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. DISCUSSION: Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.

4.
Neurology ; 96(12): e1595-e1607, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33597289

RESUMO

OBJECTIVE: To assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM). METHODS: Participants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety. RESULTS: Between November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24-104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had ≥1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively). CONCLUSION: Extended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02573467. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, well-tolerated, and did not provide meaningful functional benefit. The study is rated Class IV because of the open-label design of extension treatment period 2.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Miosite de Corpos de Inclusão/tratamento farmacológico , Acidentes por Quedas , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Miosite de Corpos de Inclusão/complicações , Tempo , Resultado do Tratamento , Teste de Caminhada
5.
Artigo em Inglês | MEDLINE | ID: mdl-33367878

RESUMO

OBJECTIVE: The current classification criteria for idiopathic inflammatory myopathy (IIM) retain PM as a major disease subgroup. However, evolution in the understanding of IIM has suggested that many of these patients could be better described as having an alternative diagnosis. In the present study, we apply the latest understanding of IIM subtyping to retrospectively review PM diagnoses in a large cohort of IIM patients. METHODS: Within a previously reported cohort of 255 patients from a UK tertiary myositis clinic, 37 patients classified as PM according to both the EULAR/ACR IIM criteria and expert opinion were identified. Clinical data and complementary tests were reviewed, and consensus decisions regarding final classification were reached in each case. RESULTS: Nine (9/37, 24.3%) patients remained classified as PM, 3.5% (9/255) of the original cohort; these PM patients were seronegative for myositis antibodies, responsive to immunosuppression, and in 4/7 (57.1%) patients where muscle biopsy was performed had HLA-1 upregulation and endomysial inflammatory infiltrates. Immune-mediated necrotizing myopathy (5/37, 13.5%) and connective tissue disease overlap myositis (7/37, 19%) were the main alternative diagnoses. The remaining patients were diagnosed as: unspecified myopathy (6/37, 16%), dermatomyositis (2/37, 5%), cancer-associated myopathy (3/37, 8.1%), and non-inflammatory myopathy (1/37, 3%, myofibrillar myopathy). Four patients (4/37, 10%) had insufficient data available to confidently reclassify. CONCLUSION: Our study confirms that PM can now be considered a rare IIM subgroup. A thorough examination, complete myositis autoantibody panel, and careful interpretation of the biopsy results is recommended to confirm the correct IIM sub-type.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33175137

RESUMO

OBJECTIVE: The COVID-19 pandemic and the subsequent effects on healthcare systems is having a significant effect on the management of long-term autoimmune conditions. The aim of this study was to assess the problems faced by patients with idiopathic inflammatory myopathies (IIM). METHODS: An anonymized eSurvey was carried out with a focus on effects on disease control, continuity of medical care, drug procurance and prevalent fears in the patient population. RESULTS: Of the 608 participants (81.1% female, median (s.d.) age 57 (13.9) years), dermatomyositis was the most frequent subtype (247, 40.6%). Patients reported health-related problems attributable to the COVID-19 pandemic (n = 195, 32.1%); specifically 102 (52.3%) required increase in medicines, and 35 (18%) required hospitalization for disease-related complications. Over half (52.7%) of the surveyed patients were receiving glucocorticoids and/or had underlying cardiovascular risk factors (53.8%), placing them at higher risk for severe COVID-19. Almost one in four patients faced hurdles in procuring medicines. Physiotherapy, critical in the management of IIM, was disrupted in 214 (35.2%). One quarter (159, 26.1%) experienced difficulty in contacting their specialist, and 30 (4.9%) were unable to do so. Most (69.6%) were supportive of the increased use of remote consultations to maintain continuity of medical care during the pandemic. CONCLUSION: This large descriptive study suggests that the COVID-19 pandemic has incurred a detrimental effect on continuity of medical care for many patients with IIM. There is concern that delays and omissions in clinical care may potentially translate to poorer outcomes in the future.

7.
BMC Rheumatol ; 4: 47, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974608

RESUMO

Background: The idiopathic inflammatory myopathies (IIMs) are chronic autoimmune conditions, typically resulting in proximal muscle weakness and impacting upon quality of life. Accurate measurement of IIM disease activity is imperative for appropriate medical management and carrying out valid clinical trials. The International Myositis Assessment and Clinical Studies Group (IMACS) "Disease Activity Core Set Measures" are the current gold-standard of IIM disease activity assessment. Anecdotally, patients with an IIM report that the IMACS Core Set Measures and other available methods do not necessarily capture their perceived disease activity. Investigating the patient experiences of living with an IIM and their views on the accuracy of the IMACS Core Set Measures will provide valuable insights for both clinical and research purposes. Methods: Eighteen interviews with patients with an IIM were carried out and analysed thematically, using a grounded theory approach. Experiences on living with an IIM and perceptions on the accuracy of disease activity measurement methods were explored. Results: Interview analysis revealed four themes: 1) fatigue, 2) pain, 3) day-to-day symptom variation, 4) limitations of creatine kinase levels and manual muscle testing. Conclusions: This study has provided valuable insights into patient experiences of living with an IIM. Aspects of IIM disease activity perceived not to be wholly measured by the IMACS Core Set Measures have also been identified. These findings have implications for future IIM clinical care and research, in particular providing justification for research into pain, fatigue and symptom variation.

8.
Rheumatol Int ; 40(12): 2047-2055, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32880031

RESUMO

The idiopathic inflammatory myopathies (IIM) are heterogeneous and lead to high morbidity and mortality. Knowledge deficits among healthcare professionals could be detrimental to clinical care. Identifying areas of deficient Knowledge, Attitude and Practice (KAP) of IIM can improve physician education and patient outcomes. To assess the proportion of physicians treating IIM with poor KAP and identify the key areas of deficit. An anonymised and validated e-survey (57 questions) was circulated among physicians treating IIM (purposive sampling). Responses were evaluated using the Likert scale for good (> 70% correct response), poor (> 20% chose > 2 answers) and the rest as intermediate consensus. Descriptive statistics were used. Intergroup comparisons were done using non-parametric tests. Of 80 (9.1% of 883) respondents, 90% were rheumatologists and 37.5% academicians. The knowledge base of treating physicians was good in specific domains such as triggers (80-90%), clinical presentation (MDA5, statin myositis, steroid myopathy, anti-synthetase syndrome) (82-92%), IIM mimics (41-89%), investigations (23-92%) and risk of osteoporosis in IIM (79%). There is also an intermediate knowledge base/consensus for outcome measures (30-56%) and response criteria (30-53%). There was poor knowledge and consensus on trials (27-34%), EULAR/ACR criteria (31%) and exercise-based interventions (17-62%). While 90% agree on the need for muscle biopsy to diagnose polymyositis, only one-third advocated it for juvenile and adult DM. Physicians have a good understanding of the triggers, clinical presentation and mimics of IIM. Poor to intermediate knowledge and consensus exists regarding muscle biopsy, outcome measures, response criteria and exercise-based interventions, which could be addressed through future focussed educational initiatives.

9.
Curr Opin Rheumatol ; 32(6): 553-561, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32890032

RESUMO

PURPOSE OF REVIEW: We have reviewed the literature to identify significant advances related to disease activity and damage in the idiopathic inflammatory myopathies (IIMs) from January 2019 to July 2020. RECENT FINDINGS: New observations in the field from 2019 to 2020 have resulted in a better understanding of the clinical association and pathogenic origins of IIM. The use of patient-reported outcome measures and perspectives, identifying biomarkers and making better use of autoantibody testing are summarized. Basic sciences have led to an improved understanding of the role of NETosis in calcinosis, and of interferon type 1, in IIM. Preliminary insights are offered into Covid-19 in the setting of IIM, and the use of potential tools for monitoring disease remotely, which may assume larger importance for optimal disease management during a global pandemic. The wider exploration of newer imaging modalities and the use of nailfold capillaroscopy is a further step in better management of the condition. SUMMARY: The summarized research in IIM is a step forward in being able to further define, and to distinguish disease activity from damage, in order to potentially aid future clinical diagnosis and management in this challenging disease.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Monitorização Fisiológica/métodos , Miosite/diagnóstico , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Comorbidade , Humanos , Miosite/epidemiologia , Pandemias
13.
BMC Rheumatol ; 4: 28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32699830

RESUMO

Background: Line blot immunoassays (LIA) for myositis-specific (MSA) and myositis-associated (MAA) autoantibodies have become commercially available. In the largest study of this kind, we evaluated the clinical performance of a widely used LIA for MSAs and MAAs. Methods: Adults tested for MSA/MAA by LIA at a tertiary myositis centre (January 2016-July 2018) were identified. According to expert-defined diagnoses, true and false positive rates were calculated for strongly and weakly positive autoantibody results within three cohorts: idiopathic inflammatory myopathy (IIM), connective tissue disease (CTD) without myositis, and non-CTD/IIM. Factors associated with true positivity were determined. Results: We analysed 342 cases. 67 (19.6%) had IIM, in whom 71 autoantibodies were detected (50 strong positives [70.4%], 21 weak positives [29.6%]). Of the strong positives, 48/50 (96.0%; 19 MSAs, 29 MAAs) were deemed true positives. Of the weak positives, 15/21 (71.4%; 3 MSAs, 12 MAAs) were deemed true positives.In CTD without myositis cases (n = 120), 31/61 (51.0%; 5 MSAs, 26 MAAs) autoantibodies were strongly positive, with 24/31 (77.4%; 0 MSAs, 24 MAAs) true positives. 30/61 (49.2%; 13 MSAs, 17 MAAs) were weakly positive, with 16/30 (53.3%; 0 MSAs, 16 MAAs) true positives. In non-CTD/IIM cases (n = 155), all 24 MSAs and 22 MAAs were false positives; these results included 17 (37.0%; 7 MSAs, 10 MAAs) strong positives.Individual autoantibody specificities were > 98.2 and > 97.5% for weakly and strongly positive results, respectively. True positivity was associated with high pre-test for IIM (odds ratio 50.8, 95% CI 13.7-189.2, p < 0.001) and strong positive (versus weak positive) results (4.4, 2.3-8.3, p < 0.001). Conclusions: We demonstrated the high specificity of a myositis LIA in a clinical setting. However, a significant burden of false positive results was evident in those with a low pre-test likelihood of IIM and for weakly positive autoantibodies.

14.
Clin Rheumatol ; 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32572804

RESUMO

OBJECTIVES: To estimate the incidence of cardiovascular (CV) events in idiopathic inflammatory myopathy (IIM) compared to patients with rheumatoid arthritis (RA) and the general population. To explore the contribution of traditional CV risk factors to any difference observed. METHODS: A retrospective matched population-based cohort study was conducted using UK Clinical Practice Research Datalink (CPRD) from 1987 to 2013. The incidence of CV events was calculated for each cohort over time and compared using Cox proportional hazards models. Multivariable analyses were used to adjust for traditional CV risk factors. RESULTS: A total of 603 patients with IIM 4047 RA and 4061 healthy controls were included. The rate of CV events in IIM was significantly greater than healthy controls [hazard ratio (HR) 1.47 (95% confidence interval (CI) 1.18-1.83)] and remained significant after adjustment for CV risk factors [HR 1.38 (95% CI 1.11-1.72)]. Risk was similar between IIM and RA [HR 1.01 (95% CI 0.78-1.31)]. The rate of myocardial infarction [HR 1.61 (95% CI 1.27-2.04)] but not stroke [HR 0.92 (95% CI 0.59-1.44)] was significantly greater in IIM compared to healthy controls. After the first 5 years, the rate of CV events for RA remained significantly greater compared to the control group, but appeared to return to that of the healthy controls in the IIM group. CONCLUSION: IIM is associated with an increased risk of CV events in the first 5 years after diagnosis similar to that of RA. Beyond 5 years, the risk appears to return to that of the general population in IIM but not RA.Key Points• The excess risk of cardiovascular events in IIM is similar to that found in RA.• The excess risk of cardiovascular events is greatest in the first 5 years after diagnosis.

15.
BMC Rheumatol ; 4: 25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32529172

RESUMO

Background: The idiopathic inflammatory myopathies (IIMs) are heterogeneous autoimmune conditions of skeletal muscle inflammation and weakness. MicroRNAs (miRNAs) are short, non-coding RNA which regulate gene expression of target mRNAs. The aim of this study was to profile miRNA and mRNA in IIM and identify miRNA-mRNA relationships which may be relevant to disease. Methods: mRNA and miRNA in whole blood samples from 7 polymyositis (PM), 7 dermatomyositis (DM), 5 inclusion body myositis and 5 non-myositis controls was profiled using next generation RNA sequencing. Gene ontology and pathway analyses were performed using GOseq and Ingenuity Pathway Analysis. Dysregulation of miRNAs and opposite dysregulation of predicted target mRNAs in IIM subgroups was validated using RTqPCR and investigated by transfecting human skeletal muscle cells with miRNA mimic. Results: Analysis of differentially expressed genes showed that interferon signalling, and anti-viral response pathways were upregulated in PM and DM compared to controls. An anti-Jo1 autoantibody positive subset of PM and DM (n = 5) had more significant upregulation and predicted activation of interferon signalling and highlighted T-helper (Th1 and Th2) cell pathways. In miRNA profiling miR-96-5p was significantly upregulated in PM, DM and the anti-Jo1 positive subset. RTqPCR replicated miR-96-5p upregulation and predicted mRNA target (ADK, CD28 and SLC4A10) downregulation. Transfection of a human skeletal muscle cell line with miR-96-5p mimic resulted in significant downregulation of ADK. Conclusion: MiRNA and mRNA profiling identified dysregulation of interferon signalling, anti-viral response and T-helper cell pathways, and indicates a possible role for miR-96-5p regulation of ADK in pathogenesis of IIM.

17.
Muscle Nerve ; 62(1): 76-82, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32134516

RESUMO

INTRODUCTION: Objective information on longitudinal disease progression in inclusion body myositis (IBM) is lacking. METHODS: Longitudinal dynamometry and functional status data were collated from a cohort of IBM patients. Annual change was calculated by means of linear modeling. Trajectories of change in grip, knee extension, IBM Functional Rating Scale (IBM-FRS) and Neuromuscular Symptom Score (NSS) were identified by means of latent growth mixture modeling. RESULTS: Data were collated from 75 IBM patients (348 person-years follow-up). Annual strength loss was greatest for pinch (-10%) and knee extension (-4%). Functional deterioration was greatest for males. Three distinct trajectory groups were identified. Rapid deterioration trajectory for grip strength was associated with younger diagnosis age. Rapid deterioration for knee extension strength was associated with older age of diagnosis. DISCUSSION: This study has quantified strength change in IBM and identified distinct trajectory groups, which will aid prognostication and stratification for inclusion into future clinical trials.


Assuntos
Progressão da Doença , Dinamômetro de Força Muscular/tendências , Força Muscular/fisiologia , Miosite de Corpos de Inclusão/diagnóstico , Miosite de Corpos de Inclusão/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Força da Mão/fisiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Estudos Prospectivos
18.
Nat Rev Rheumatol ; 16(6): 299-300, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32221511
19.
Best Pract Res Clin Rheumatol ; 34(1): 101486, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32063440

RESUMO

The idiopathic inflammatory myopathies are a group of heterogeneous autoimmune connective tissue diseases. Despite increase in the understanding of these conditions, securing a timely diagnosis and accurate subtype classification remains difficult in some cases. This has important implications for patients, where delayed or inappropriate treatments can have a negative effect on outcomes. Several conditions can mimic myositis, including metabolic myopathies, genetic myopathies and neurological disease. In addition, the heterogeneity within the idiopathic inflammatory myopathy spectrum can also create diagnostic confusion, referred to here as 'myositis chameleons'. This includes inclusion body myositis, immune-mediated necrotizing myopathy, hypomyopathic variants of anti-synthetase syndrome and overlap disease. We highlight the importance of a thorough diagnostic workup, refer to updated classification criteria and emphasize the importance of myositis autoantibody testing. Where diagnostic doubt exists, the involvement of a specialist centre and a multidisciplinary team is vital.


Assuntos
Doenças Autoimunes , Miosite de Corpos de Inclusão , Miosite , Autoanticorpos , Doenças Autoimunes/diagnóstico , Humanos , Miosite/diagnóstico
20.
Rheumatology (Oxford) ; 59(5): 1026-1030, 2020 05 01.
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.


Assuntos
Autoantígenos/imunologia , Progressão da Doença , Fator de Iniciação 3 em Eucariotos/sangue , Polimiosite/imunologia , Adulto , Autoanticorpos/sangue , Biomarcadores/sangue , Western Blotting/métodos , Estudos de Casos e Controles , Fator de Iniciação 3 em Eucariotos/imunologia , Feminino , Humanos , Imunoprecipitação/métodos , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Polimiosite/tratamento farmacológico , Polimiosite/fisiopatologia , Valores de Referência , Estudos Retrospectivos , Febre Reumática/imunologia , Febre Reumática/fisiopatologia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia
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