Novel autoantibodies and clinical phenotypes in adult and juvenile myositis

Autoantibodies targeting intracellular proteins involved in key processes are detected in patients with idiopathic inflammatory myopathies. These myositisspecific autoantibodies have been increasingly demonstrated to correlate with distinct clinical phenotypes within the myositis spectrum. This review highlights the clinical associations of the myositisspecific autoantibodies, with particular attention to the recently identified and characterized novel myositis autoantibodies: p155/140, p140 (MJ), CADM-140 (MDA5), SAE, and 200/100

The reliability of immunoassays to detect autoantibodies in patients with myositis is dependent on autoantibody specificity

OBJECTIVES: In order to address the reliability of commercial assays to identify myositis-specific and -associated autoantibodies, we aimed to compare the results of two commercial immunoassays with the results obtained by protein immunoprecipitation.METHODS: Autoantibody status was determined using radio-labelled protein immunoprecipitation for patients referred to our laboratory for myositis autoantibody characterization. For each autoantibody of interest, the sera from 25 different patients were analysed by line blot (Euroline Myositis Antigen Profile 4, EuroImmun, Lübeck, Germany) and dot blot (D-Tek BlueDiver, Diagnostic Technology, Belrose, NSW, Australia). Sera from 134 adult healthy controls were analysed.RESULTS: Overall commercial assays performed reasonably well, with high agreement (Cohen's κ &gt;0.8). Notable exceptions were the detection of rarer anti-synthetases with κ &lt; 0.2 and detection of anti-TIF1γ, where κ was 0.70 for the line blot and 0.31 for dot blot. Further analysis suggested that the proportion of patients with anti-TIF1γ may recognize a conformational epitope, limiting the ability of blotting-based assays that utilize denatured antigen to detect this clinically important autoantibody. A false-positive result occurred in 13.7% of samples analysed by line blot and 12.1% analysed by dot blot.CONCLUSION: The assays analysed do not perform well for all myositis-specific and -associated autoantibodies and overall false positives are relatively common. It is crucial that clinicians are aware of the limitations of the methods used by their local laboratory. Results must be interpreted within the clinical context and immunoprecipitation should still be considered in selected cases, such as apparently autoantibody-negative patients where anti-synthetase syndrome is suspected.</p

Investigation of myositis and scleroderma specific autoantibodies in patients with lung cancer

BACKGROUND: The close temporal association between onset of some connective tissue diseases and cancer suggests a paraneoplastic association. Adult patients with scleroderma with anti-RNA polymerase III autoantibodies and adult patients with dermatomyositis with anti-transcriptional intermediary factor 1 (anti-TIF1) or anti-nuclear matrix protein 2 (anti-NXP2) autoantibodies have a significantly increased risk of developing cancer. Autoantibodies may serve as biomarkers for early detection of cancer and also could be relevant for prediction of responses to immune therapies. We aimed to test whether myositis and scleroderma specific or associated autoantibodies are detectable in individuals with lung cancer.METHODS: Serum from 60 Caucasian patients with lung cancer (30 with small cell lung cancer, 30 with non-small cell lung cancer) was screened for myositis and scleroderma specific and associated autoantibodies by radiolabelled immunoprecipitation.RESULTS: Anti-TIF1, anti-NXP2 or anti-RNA polymerase III autoantibodies were not detected in any of the 60 patients with lung cancer. Anti-glycyl-transfer RNA (tRNA) synthetase (anti-EJ) autoantibodies were detected in one patient with non-small cell lung cancer. No other known myositis or scleroderma autoantibodies were identified.CONCLUSIONS: Myositis and scleroderma specific autoantibodies, including anti-TIF1, anti-NXP2 and anti-RNA polymerase III, are rare in patients with lung cancer without an autoimmune disease. We report here the first case of anti-EJ autoantibodies being detected in a patient with lung cancer without clinical or radiographic evidence of the anti-synthetase syndrome.</p

Presence of anti-eukaryotic initiation factor-2B, anti-RuvBL1/2 and anti-synthetase antibodies in patients with anti-nuclear antibody negative systemic sclerosis

Objectives: Autoantibodies targeting ubiquitously expressed nuclear antigens can be identified in most patients with SSc. Cytoplasmic autoantibodies (in otherwise ANA-negative sera) targeting eukaryotic initiation factor-2B (anti-eIF2B) have recently been identified in SSc with clinical associations to dcSSc disease and interstitial lung disease (ILD), although the majority of samples originated from a tertiary SSc-ILD centre. We investigated the prevalence and clinical associations of recently described SSc-specific (including anti-eIF2B) and other cytoplasmic autoantibodies in ANA-negative sera obtained from a large representative SSc cohort.Methods: ANA-negative sera from the Scleroderma Family Registry and DNA Repository underwent indirect immunofluorescence, radiolabelled protein immunoprecipitation (± immunodepletion) to identify anti-eIF2B and other CTD-related autoantibodies. The clinical phenotype of positive samples was evaluated.Results: Immunoprecipitation was performed on 128 ANA-negative samples (obtained from 3249 SSc patients). Anti-eIF2B antibodies were present in nine patients (7%), the majority of whom had dcSSc (8/9). SSc-ILD was present in all anti-eIF2B patients for whom chest imaging was available (7/9). Anti-synthetase autoantibodies (targeting PL12, PL7, OJ and Zo) were identified in seven patients (5.5%), all of whom fulfilled the 2013 ACR/EULAR classification criteria for SSc and had evidence of SSc-ILD where relevant outcomes were available for evaluation. Anti-RuvBL1/2 antibodies were identified in two patients with SSc-overlap syndromes.Conclusion: Anti-eIF2B antibodies are cytoplasmic SSc-specific autoantibodies with strong clinical associations with dcSSc and SSc-ILD found in ANA-negative sera. Anti-synthetase autoantibodies, and other recently discovered SSc-specific antibodies such as anti-RuvBL1/2, can also be identified in ANA-negative SSc.</p

Presence of anti-eukaryotic initiation factor-2B, anti-RuvBL1/2 and anti-synthetase antibodies in patients with anti-nuclear antibody negative systemic sclerosis

Objectives: Autoantibodies targeting ubiquitously expressed nuclear antigens can be identified in most patients with SSc. Cytoplasmic autoantibodies (in otherwise ANA-negative sera) targeting eukaryotic initiation factor-2B (anti-eIF2B) have recently been identified in SSc with clinical associations to dcSSc disease and interstitial lung disease (ILD), although the majority of samples originated from a tertiary SSc-ILD centre. We investigated the prevalence and clinical associations of recently described SSc-specific (including anti-eIF2B) and other cytoplasmic autoantibodies in ANA-negative sera obtained from a large representative SSc cohort.Methods: ANA-negative sera from the Scleroderma Family Registry and DNA Repository underwent indirect immunofluorescence, radiolabelled protein immunoprecipitation (± immunodepletion) to identify anti-eIF2B and other CTD-related autoantibodies. The clinical phenotype of positive samples was evaluated.Results: Immunoprecipitation was performed on 128 ANA-negative samples (obtained from 3249 SSc patients). Anti-eIF2B antibodies were present in nine patients (7%), the majority of whom had dcSSc (8/9). SSc-ILD was present in all anti-eIF2B patients for whom chest imaging was available (7/9). Anti-synthetase autoantibodies (targeting PL12, PL7, OJ and Zo) were identified in seven patients (5.5%), all of whom fulfilled the 2013 ACR/EULAR classification criteria for SSc and had evidence of SSc-ILD where relevant outcomes were available for evaluation. Anti-RuvBL1/2 antibodies were identified in two patients with SSc-overlap syndromes.Conclusion: Anti-eIF2B antibodies are cytoplasmic SSc-specific autoantibodies with strong clinical associations with dcSSc and SSc-ILD found in ANA-negative sera. Anti-synthetase autoantibodies, and other recently discovered SSc-specific antibodies such as anti-RuvBL1/2, can also be identified in ANA-negative SSc.</p

Identification of a novel autoantigen eukaryotic initiation factor 3 associated with polymyositis

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Dermatomyositis-specifikus autoantitesttel rendelkező és autoantitest-negatív betegeink klinikai jellemzőinek és laboratóriumi paramétereinek összehasonlítása

Absztrakt Bevezetés: A myositisek a proximalis végtagizmok gyengeségével jellemezhető autoimmun betegségek. Célkitűzés: A szerzők célul tűzték ki a dermatomyositis-specifikus antitestek (anti-Mi-2, anti-transcriptional intermediary factor 1 gamma, anti-nuclear matrix protein 2, anti-small ubiquitin-like modifier activating enzyme, anti-melanoma differentiation-associated gene 5) gyakoriságának felmérését hazai myositises populációban. Klinikai jellemzőiket és laboratóriumi paramétereiket összehasonlították a myositisspecifikus antitesttel nem rendelkező betegek adataival. Módszer: Az autoantitest-meghatározás immunoblottal, illetve immunprecipitációval történt. Eredmények: 330 myositises beteg közül 48 dermatomyositis-specifikus autoantitest-pozitív beteg adatait dolgozták fel és elemezték retrospektív módon. A vizsgált antitestek összességében ritkábban fordultak elő a vizsgált magyar populációban, mint a nemzetközi tanulmányokban. Megfigyelték, hogy a dermatomyositis-specifikus antitesttel rendelkező betegeknél jellemző volt az akut, súlyosabb izomgyengeséggel járó kezdet, amely a legtöbb esetben jellegzetes bőrtünetekkel társult. Következtetések: A myositisspecifikus antitestek meghatározása segítséget ad a beteg tüneteinek differenciálásában, felvilágosítást nyújt a várható lefolyásról és segítheti a megfelelő terápia megválasztását. Orv. Hetil., 2015, 156(36), 1451–1459

Risk factors for cancer in patients with myositis. Clinical, immunological characteristics and the role of the anti-p155/140 antibody

Introduction: Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by progressive proximal muscle weakness. Cancer-associated myositis represents the worst prognostic group within this heterogeneous disease. Aim: The aim of this study was to reveal factors which increase the risk factors for association of cancerous disease in patients with myositis. Furthermore, the authors explored the most common types of associated malignancies in their patients with myositis and characterize the clinical findings in a sub-group of anti-p155/140 positive patients. Method: In this retrospective study, myositis patients with and without associated cancer were analysed (32 and 64 patients, respectively). In addition, anti-p155/140 positive and negative groups were compared, irrespective to the presence of associated malignancies. Results: The risk for associated malignancy was higher in patients with severe muscle and skin symptoms and those with dermatomyositis. Furthermore, increased risk for malignancy was noted in the presence of particular skin symptoms and the absence of systemic symptoms. The anti-p155/140 antibody was proved to be a feasible marker of an independent clinical sub-group which overlapped clinical characteristics with cancer-associated myositis. Conclusions: These results may help the identification of patients with myositis with a higher risk for associated malignancy. Orv. Hetil., 2014, 155(36), 1437–1444.</jats:p