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


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.

Rheumatology (Oxford) ; 53(4): 644-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24310298


OBJECTIVES: Pulmonary disease is a rare complication in JDM, described in only a few studies. This long-term follow-up study aimed to (i) describe pulmonary involvement in a national cohort of JDM patients estimated by conventional spirometry, (ii) compare pulmonary impairment with overall JDM outcome, and (iii) identify possible associations between pulmonary impairment and myositis-specific autoantibodies (MSAs). METHODS: Fifty-one JDM patients performed conventional spirometry in a cross-sectional follow-up study. The scores of the Myositis Damage Index (MDI), Myositis Damage by visual analogue scale (MYODAM-VAS) and physician's global damage assessment were used to estimate JDM outcome. ANAs, MSAs and myositis-associated autoantibodies were analysed in all patients. RESULTS: Forty-two patients (82%) (mean follow-up time 14.3 years) had normal lung function. Four patients (8%) were diagnosed with JDM-related restrictive interstitial lung disease. No patients reported pulmonary symptoms. Patients with restrictive pulmonary function had increased long-term damage estimated by MDI (P = 0.008), MYODAM-VAS (P = 0.04), global assessment (P = 0.03) and number of organ systems involved (P = 0.009). We found significant correlation between the restrictive pulmonary function test and damage by the MDI (r = 0.43, P = 0.003), MYODAM-VAS (r = 0.44, P = 0.002), and global damage assessment (r = 0.43, P = 0.003). No association was found between the restrictive pulmonary function test and autoantibodies. CONCLUSION: In a long-term follow-up study of JDM patients, the majority of patients demonstrated normal lung function. However, restrictive pulmonary impairment was identified in 8% of patients, indicating a need for repetitive pulmonary follow-up in JDM patients. Restrictive pulmonary involvement was associated with increased long-term JDM damage.

Autoanticorpos/imunologia , Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/imunologia , Adolescente , Adulto , Anticorpos Antinucleares/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Dermatomiosite/complicações , Dermatomiosite/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ribonucleoproteínas/imunologia , Índice de Gravidade de Doença , Espirometria , Capacidade Vital , Adulto Jovem
Rheumatology (Oxford) ; 52(2): 287-95, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23001614


OBJECTIVES: It has previously been shown that patients with active JDM have decreased aerobic fitness; however, it is not known whether these patients regain their physical fitness after recovery. The objective of this study was to investigate the long-term outcome of aerobic fitness in patients with JDM. We hypothesized that fitness (VO(2max)) is reduced compared with healthy controls in the years after active JDM. METHODS: A maximal exercise test was performed using a cycle ergometer. Results were compared with those of sex- and age-matched healthy controls. RESULTS: A total of 36 patients with JDM in remission were included, 2-36 years after disease onset. Twelve patients (33%) had normal VO(2max) and 24 patients (67%) had decreased VO(2max). Mean VO(2max) was higher in the healthy controls vs patients (P < 0.001, 95% CI -10.7, -4.4). A significant difference between patients with JDM and controls was observed for women (P < 0.001), men (P = 0.04), children < 18 years (P = 0.002) and adults > 18 years (P = 0.01). The decreased VO(2max) was independent of the duration of remission, but it was associated with the duration of active disease. By linear regression, it was revealed that for every year of active disease, VO(2max) was reduced by 0.85 ml/min/kg on average (P < 0.001). CONCLUSION: This long-term follow-up study demonstrates that patients who have had JDM have persistently impaired fitness. This impairment is directly related to the duration of active disease.

Dermatomiosite/fisiopatologia , Exercício/fisiologia , Consumo de Oxigênio/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Dermatomiosite/terapia , Eletrocardiografia , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Indução de Remissão , Testes de Função Respiratória , Índice de Gravidade de Doença , Adulto Jovem