RESUMEN
OBJECTIVES: To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. METHODS: Adult patients with confirmed IIM recruited to the EuroMyositis registry (nâ¯=â¯1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. RESULTS: MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2-7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (pâ¯<â¯0.001) with cutaneous involvement. Anti-TIF1 and anti-Mi-2 positive patients had an increased risk of malignancy (OR 4.67 and 2.50 respectively), and anti-SRP patients had a greater likelihood of cardiac involvement (OR 4.15). Interstitial lung disease was strongly associated with the anti-tRNA synthetases, anti-MDA5, and anti-U1RNP/Sm. Overlap disease was strongly associated with anti-PMScl, anti-Ku, anti-U1RNP/Sm and anti-Ro60. Absence of MSA/MAA was negatively associated with extra-muscular manifestations. CONCLUSIONS: Myositis autoantibodies are present in the majority of patients with IIM and identify distinct clinical subsets. Furthermore, MSAs are nearly always mutually exclusive endorsing their credentials as valuable disease biomarkers.
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Autoanticuerpos/inmunología , Susceptibilidad a Enfermedades/inmunología , Miositis/epidemiología , Miositis/inmunología , Adulto , Anciano , Estudios de Cohortes , Comorbilidad , Dermatomiositis/epidemiología , Dermatomiositis/inmunología , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miositis/diagnóstico , Oportunidad Relativa , Polimiositis/epidemiología , Polimiositis/inmunología , PrevalenciaRESUMEN
AIM: Juvenile idiopathic inflammatory myopathies have been recently reclassified into clinico-serological subgroups. Myopathological correlates of the subgroups are incompletely understood. METHODS: We studied muscle biopsies from 101 children with clinically and serologically defined juvenile idiopathic inflammatory myopathies from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review and C5b-9 complement analysis. RESULTS: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti-TIF1γ, 15/90 anti-NXP2, 11/90 anti-MDA5, 5/90 anti-Mi2 and 6/90 anti-PmScl. JDM biopsy severity scores were consistently low in the anti-MDA5 group, high in the anti-Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage-rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101) and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b-9-deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b-9 deposition. CONCLUSION: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes.
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Autoanticuerpos/inmunología , Miositis/inmunología , Miositis/patología , Autoantígenos/inmunología , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , FenotipoRESUMEN
AIMS: To evaluate the relationship between expression of myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis-specific autoantibodies (MSA) status in JDM patients. METHODS: 103 patients (median aged 6.3, interquartile range 0.5-15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored. Clinical data at initial presentation were collected and autoantibodies were analysed. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity, and MSA status. RESULTS: Expression of MxA protein on JDM samples was identified in 61.2%. There was a significant association between MxA scores and Childhood Myositis Assessment Scale (CMAS) (P = 0.002), and Manual Muscle Testing of Eight Muscles (MMT8) (P = 0.026). CMAS and MMT8 scores were significantly lower in the group of patients with strong MxA expression. MxA scores differed according to MSA subgroups (P = 0.002). Patients with positive nuclear matrix protein 2 autoantibodies had strong MxA expression, whereas anti-melanoma differentiation-associated gene 5 positive patients had no or weak MxA expression. CONCLUSIONS: This study reveals the significant association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients and MSA status. This confirms type I interferonopathies in muscle fibres of JDM patients which could help with improving treatment outcome in JDM patients and underscoring the distinct pathophysiological pathways in different MSA status.
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Dermatomiositis/metabolismo , Enfermedades Musculares/inmunología , Miositis/metabolismo , Proteínas de Resistencia a Mixovirus/metabolismo , Adolescente , Autoanticuerpos/metabolismo , Biomarcadores/análisis , Niño , Preescolar , Estudios de Cohortes , Dermatomiositis/inmunología , Femenino , Humanos , Lactante , Masculino , Miositis/inmunología , Proteínas de Resistencia a Mixovirus/inmunologíaRESUMEN
BACKGROUND: Anti-Signal Recognition Particle associated myopathy is a clinically and histopathologically distinct subgroup of Juvenile Idiopathic Inflammatory Myositis, which is under-recognised in children and fails to respond to conventional first line therapies. We present three cases where remission was successfully induced using combination therapy with intensive rehabilitation. CASE PRESENTATIONS: Three new patients are reported. All 3 cases presented with profound, rapid-onset, proximal myopathy and markedly raised CK, but no rash. Histology revealed a destructive myopathy characterized by scattered atrophic and necrotic fibres with little or no inflammatory infiltrate. All 3 patients responded to induction with cyclophosphamide, IVIG and rituximab, in conjunction with intensive physiotherapy and methotrexate as the maintenance agent. Our patients regained near-normal strength (MMT > 70/80), in contrast with the current literature where >50% of cases reported severe residual weakness. A literature search on paediatric anti-SRP myositis was performed to June 2016; PubMed was screened using a combination of the following terms: signal recognition particle, autoantibodies, antibodies, myositis, muscular diseases, skeletal muscle, childhood, paediatric, juvenile. Articles in a foreign language were excluded. Nine case studies were found. CONCLUSION: This paper supports the hypothesis that anti-SRP myositis is distinct from other JIIM. It is an important differential to JDM and should be considered where there is severe weakness without rash or if highly elevated muscle enzymes (CK > 10,000 U/l) are found. Early identification is essential to initiate aggressive medical and physical therapy. Greater international collaboration and long-term follow-up data is needed to establish the most effective treatment strategy for this rare group of patients.
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Músculo Esquelético/patología , Miositis/diagnóstico , Partícula de Reconocimiento de Señal/antagonistas & inhibidores , Adolescente , Autoanticuerpos/inmunología , Niño , Ciclofosfamida/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Metotrexato/uso terapéutico , Miositis/patología , Miositis/terapia , Rituximab/uso terapéutico , Resultado del TratamientoRESUMEN
AIM: The aim of this study is to determine whether the analysis of CD38 expression by chronic lymphocytic leukaemia (CLL) cells provides useful additional prognostic information. METHODS: Clinical, laboratory, overall survival (OS) and treatment-free survival (TFS) data were collected on 130 CLL patients who had CD38 expression analysed at Canterbury Health Laboratories, New Zealand (NZ) during 1998-2008. RESULTS: The detection of any level of CD38 expression by CLL cells was associated with a significantly shorter OS and TFS. When analysis was restricted to Binet stage A patients, CD38 expression identified a subset of patients (21%) who, in common with Binet stage B/C patients, had a significantly shorter OS and TFS (P<0.0015), and a TFS at 4 years of <10%. In contrast, CD38-negative Binet stage A patients had an OS that was not significantly different from that of an age/sex-matched NZ population and a 5-year TFS of 77%. CONCLUSION: This study indicates that, when combined with clinical staging, the presence of any detectable CD38 expression can be used to further improve the identification of CLL patients with more aggressive disease (i.e. Binet stage B/C or Binet stage A and CD38 positive). This will allow better identification of those patients requiring more intensive monitoring and also allow improved patient counselling regarding prognosis.