|Year : 2020 | Volume
| Issue : 6 | Page : 74-80
Bye-bye muscle biopsy, we have autoantibodies with us now
Victoria Riddell1, Sarah L Tansley2
1 Department of Biology and Biochemistry, University of Bath, Bath, England, UK
2 Department of Pharmacy and Pharmacology, University of Bath, Bath, England, UK
|Date of Submission||01-May-2020|
|Date of Acceptance||07-Jun-2020|
|Date of Web Publication||18-Jan-2021|
Dr. Sarah L Tansley
University of Bath, Bath
Source of Support: None, Conflict of Interest: None
Muscle biopsy is generally considered the gold standard diagnostic tool for patients with presenting with features suggestive of idiopathic inflammatory myopathy. Muscle biopsy is however an invasive test, the histopathological findings can be influenced by previous treatment and not all patients with myositis spectrum disease have muscle involvement. Myositis specific and associated autoantibodies can now be identified in the majority of patients with myositis. When present they identify homogeneous patient subgroups and have the potential to be key tools in developing a personalised approach to disease management. Here we review the utility of myositis specific and associated autoantibodies as diagnostic and prognostic tools.
Keywords: Autoantibody, biopsy, diagnosis, myopathy, myositis
|How to cite this article:|
Riddell V, Tansley SL. Bye-bye muscle biopsy, we have autoantibodies with us now. Indian J Rheumatol 2020;15:74-80
| Introduction|| |
The idiopathic inflammatory myopathies (IIM) are multisystem diseases. The presenting disease features are variable but include skin disease and muscle weakness in addition to systemic features, such as fever, fatigue, and weight loss. Patients are traditionally divided into two subgroups: polymyositis and dermatomyositis depending on the presence or absence of skin disease and a third subgroup, inclusion body myositis (IBM), describes a very different group of patients with slowly progressive symptoms involving distal musculature which fail to respond to immunosuppressive medication. This classification system fails to adequately describe all the variation seen in these diseases, both in terms of clinical features and disease outcomes.,, While muscle inflammation is a defining feature of these diseases and muscle weakness is typically a prominent feature at disease presentation, amyopathic dermatomyositis, defined as the presence of pathognomonic cutaneous lesions in the absence of muscle involvement, is well described. Similarly, patients may have mild or progressive muscle disease that is not detected on initial assessment. Patients may also present with severe disease affecting other organ systems such as skin or lung disease, which may reduce the chance of IIM being considered early as a diagnosis. The heterogeneous nature of IIM creates a diagnostic challenge, not least because patients can present to a number of different medical specialties.
| Diagnosis of Idiopathic Inflammatory Myopathies|| |
Useful diagnostic tests depend on the organ systems affected, for those with muscle involvement elevated serum muscle enzymes and/or an increased T2/STIR signal on MRI suggesting muscle edema can be helpful findings but are both nonspecific and are also found in other conditions. Muscle biopsy is a well-established tool for the diagnosis of IIM and is generally considered to be the gold standard. It does, however, have a number of limitations. Not least that muscle biopsy is unlikely to be helpful in patients without muscle involvement. Furthermore, the histopathological findings can be directly influenced by any on-going or previous treatments, such as steroids. Findings can be nonspecific, or inconclusive, and muscular damage often appears similar across clinical myositis subsets, making it difficult to correctly provide a more specific diagnosis. IBM and polymyositis can be challenging to distinguish clinically and histologically, particularly early in the disease course. Indeed classical histopathological features of IBM, such as rimmed vacuoles, are absent in 20% of patients with typical clinical features. Nonetheless, muscle biopsy is helpful in excluding muscular dystrophies and other muscle disorders with overlapping clinical features. A biopsy result consistent with IIM provides a significant degree of diagnostic certainty and reports can be enhanced by systems developed to allow a standardized approach to interpretation which should facilitate the identification of homogeneous patient subgroups. Recently, published classification criteria for myositis endorsed by ACR and EULAR utilize muscle biopsy findings, laboratory features, and clinical features to determine the probability of myositis. A web-calculator for the criteria has been set up: http://www.imm.ki.se/biostatistics/calculators/iim/. The performance of these criteria is greatly enhanced where muscle biopsy data are available and can be included.
| Autoantibodies for the Diagnosis of Idiopathic Inflammatory Myopathies|| |
Autoantibodies are a hallmark feature of the autoimmune connective tissue diseases and IIM is no exception. An autoantibody can be identified in approximately 60% of patients, and have been proposed as means of diagnosing and sub-classifying affected patients. “Myositis-specific autoantibodies” (MSA) are exclusively found in patients with IIM, whereas “Myositis-associated autoantibodies” (MAA) can also be identified in both patients with IIM and other connective tissue diseases. MSA occur together only extremely rarely and are considered to be mutually exclusive while MAA may be found in conjunction with a MSA or another MAA., As a diagnostic tool, MSA/MAA have limitations: They are not present in all patients meaning that the absence of a MSA or MAA does not exclude myositis as a diagnosis. The identification of a MSA can increase diagnostic confidence, particularly where the biopsy findings are atypical or unusual. This was reported after examination of biopsy's taken alongside tests for anti-HGMCR antibody.
| Autoantibodies to Predict the Prognosis in Idiopathic Inflammatory Myopathies|| |
Perhaps the real advantage of MSA is that, where present, they divide patients into homogeneous subsets and provide a degree of phenotypic refinement not possible with other classification systems. The detailed phenotypic information provided by MSA subsets allows doctors to provide more detailed prognostic information to patients and their families and to plan further investigation and monitoring for anticipated complications. Identified MSA subsets are described in 1, which presents the known associated clinical features with each MSA.
Myositis autoantibodies are strongly associated with distinct clinical phenotypes and provide the treating physician with useful information which can then inform the approach to disease management. The clinical features associated with MSA in juvenile IIM can vary from adult IIM. For example, anti-TIf1-γ and anti-NXP2 strongly associated with malignancy in adult IIM patients. More than 50% of adult patients with the MSA anti-TIf1-γ have an associated cancer and anti-TIf1-γ associated malignancy has been demonstrated to occur exclusively in the 3-year period on either side of myositis onset,, The identification of this MSA can prompt careful cancer screening. In contrast, these autoantibodies are the most common MSA in predominantly Caucasian juvenile IIM cohorts,, yet no association with malignancy has been identified. It is not clear to what extent the differences observed between adult and juvenile MSA relate to different phenotypes associated with the MSA and the influence of age at disease onset. The association between anti-TIF1-γ is the highest risk in those over 39 years of age, yet the distinction between juvenile and adult IIM is typically either 16 or 18 years. A more detailed discussion of the clinical and serological features of adult versus juvenile IIM can be found in Tansley et al.
The major causes of mortality in patients with IIM are infection, mostly pneumonia, and malignancy, along with cardiac and lung complications. MSA can help identify those patients at high risk so appropriate interventions can be taken early, hopefully reducing both subsequent mortality and morbidity.,,, The recommendation that those patients with cancer associated MSA be subjected to cancer-specific screening appears justified and sensible. Recent evidence suggests that ovarian cancer is a particular concern in those with anti-TIF1-γ and the detection of this MSA could therefore also inform the nature of screening that is undertaken. A comprehensive investigation of lung disease in myositis patients identified that over 75% of all patients carried an MSA, predominantly an anti-synthetase MSA, or anti-MDA5. Comparing the clinical characteristics of the lung disease in these two MSA subgroups revealed that the anti-MDA5 patients had an increased risk of respiratory failure with a more acute onset of interstitial lung disease (ILD), while the identification of an anti-synthetase MSA could indicate a more positive prognosis.
MSA can also be helpful in identifying those patients with IIM presenting with predominantly extra-muscular disease. ILD, in the absence of any extra-pulmonary features can occur as a formefruste of IIM. These patients can be misdiagnosed as idiopathic ILD. Anti-Jo-1, targeting histidyl tRNA synthetase, is the most common MSA and can be identified in 15%–30% of adults with IIM., It is associated with the anti-synthetase syndrome; a well-described clinical syndrome consisting of myositis, ILD, nonerosive arthritis, Raynaud's phenomenon, fever, and characteristic skin changes termed “mechanics” hands. Seven further tRNA synthetase MSA have been reported; anti-PL7 (threonyl), anti-PL12 (alanyl), anti-OJ (isoleucyl), anti-KS (asparginyl), anti-EJ (glycyl), anti-Zo (phenylalanyl), and anti-Ha (tyrosyl) these are rarer, collectively occurring in 10%–20% of cases., The anti-synthetase syndrome can be incomplete and disease presentation varies depending on the autoantibody: While muscle disease is common in patients with myositis autoantibodies anti-Jo1, anti-PL-7, or anti-EJ, patients with anti-PL-12, anti-KS or anti-OJ in contrast often have lung dominant disease. The distinction between idiopathic ILD and IIM associated ILD is of the upmost clinical importance as, while immunosuppressive drugs are the mainstay of treatment in IIM, these are not only ineffective in idiopathic ILD but cause harm. Anti-synthetase MSA were retrospectively identified in 6.6% of a Japanese cohort with idiopathic ILD, none of whom displayed any extra-pulmonary features. A Canadian study retrospectively analyzed 165 patients referred for investigation of ILD and identified an MSA in 26.7%. Furthermore, as a consequence of MSA screening 8.5% of patients tested received a change in the diagnosis. Of those patients whose the diagnosis was altered as the result of MSA testing, 1.8% had undergone a surgical lung biopsy and 1.2% had received treatment with anti-fibrotic therapy, demonstrating the significant benefits earlier screening could have had for these patients. Interestingly, in addition to the different MSA associated with ILD described in [Table 1], the MAA anti-Ro52 has also been shown to increase patients underlying risk of ILD, even in those autoantibody subgroups not considered to be associated with ILD. The presence of anti-Ro52 alongside anti-Jo1 may suggest a higher risk of more severe pulmonary involvement as the disease progresses and analysis of a Japanese cohort suggested that the presence of both anti-Ro52 and anti-Jo1 could be linked to a distinct clinical subset. Further research is need to improve our understanding of this and other factors, which modify MSA associated phenotype including age at disease onset, ethnicity, and the environment.
|Table 1: Myositis specific autoantibodies and their clinical associations|
Click here to view
Antibody detection can clearly be used to provide crucial prognostic information; however, MSA status should always be interpreted in the appropriate clinical context and in conjunction with other investigations and clinical findings. The combination of muscle biopsy findings and MSA status can be valuable: When juvenile DM patient biopsy samples were analysed and scored for severity, and the results analyzed in conjunction with MSA status findings not only did muscle biopsy scores vary according to MSA subgroup, but when the effects of the MSA were accounted for, increased severity of muscle biopsy features was predictive of a higher risk of remaining on the treatment. Similarly, an autoantibody result is only as reliable as the testing method used and a positive result not in keeping with the clinical picture should be interpreted with caution.
| Autoantibodies to Guide Treatment in Idiopathic Inflammatory Myopathies|| |
The evidence base for pharmacological therapies in IIM is extremely limited, but in practice, the majority of patients receive treatment with a prednisolone plus a steroid sparing agent such as methotrexate or azathioprine. Agents such as IVIg, rituximab, and cyclophosphamide are typically reserved for those with severe or refractory disease. This approach is arguably simplistic for such a diverse and heterogeneous disease and the ability to stratify patients with myositis in such a way as to allow a more personalized approach to treatment is highly desirable. Certain MSA are more likely to be resistant to standard treatment approaches and this has been extrapolated to suggest these patients may benefit from a more “aggressive” treatment approach.,, More intensive immunosuppression generally carries an increased risk of adverse events, and MSA can help ensure this is targeted appropriately. Hence, called triple therapy, a combination of corticosteroids, cyclophosphamide, and tacrolimus has been shown to be beneficial in patients with rapidly progressive–ILD associated with anti-MDA5. Indeed, not receiving this combination as initial treatment was linked to poor outcomes in a Japanese cohort.,, Undoubtedly, the diagnostic certainty provided by a positive myositis autoantibody can empower the physicians to escalate treatment in a patient not responding adequately to standard therapy and can prevent unnecessary further investigation to confirm the diagnosis. It is as yet, however, unclear if and how autoantibody status should influence recommended pharmacological treatment. The rituximab in myositis study was a randomized controlled trial, investigating the benefit of rituximab in patients with refractory myositis. Sub-group analysis of this study demonstrated a differential treatment response to rituximab dependant on MSA status., The presence of an anti-synthetase, anti-Mi-2, or another MSA predicted a shorter time to improvement compared to MSA-negative patients. Based on these findings, in the UK, NHS England guidance on the use of rituximab in patients with myositis stipulates the presence of a myositis relevant autoantibody to access the drug. Consensus-based recommendations for the management patients with juvenile-onset myositis published in 2017 do not recommend MSA for risk stratification but do acknowledge that these can be helpful where available. It will be important that future clinical trials investigating treatments in patients with myositis adjust for MSA status in order to prevent confounding, due to potentially different treatment responses between MSA subgroups.
| Challenges in Autoantibody Testing|| |
A key limitation of the use of MSA in the clinical practice is the availability of testing. Immunoprecipitation is considered the reference standard method for MSA identification. It has been used to identify novel MSA, and MSA specificity can subsequently be confirmed using immunoprecipitation blotting or mass spectrometry., Immunoprecipitation is, however, an impractical method for widespread diagnostic use; it is expensive, low throughput, and specialist facilities along with staff expertise are required. Consequently, the use of immunoprecipitation for diagnostic purposes is limited to a handful of specialist centers worldwide. With the growing interest in the use of MSA for the diagnosis and planning treatment, a number of commercial assays have been developed utilizing different immunological techniques. These assays facilitate the rapid detection of MSA inexpensively and without the need for specialist expertise. A major challenge with these assays has been validation. Myositis is a rare disease and some MSA are very rare within myositis cohorts: For example, some of the anti-synthetase MSAs included in commercial immunoassays are found in just 0.3% of myositis patients, making assay validation a significant challenge. We and others have raised the concerns regarding the sensitivity of commercial immunoassays to detect the some key MSA., The features of the MSA themselves may restrict the types of immunoassay that can be used. In the original description of anti-TIF1-γ (p155) in dermatomyositis by Targoff et al. reported the presence of a conformational epitope in a significant proportion of patients. This limits the utility of popular immunoblotting based assays which use denatured antigen. Interestingly, a similar phenomenon was also observed with MSA directed against anti-OJ for which we have also shown immunoblotting assays perform particularly poorly.,
False-positive rates may be unacceptably high with commercial immunoassays, with one study reporting antibody positivity in 17% of healthy controls.,,,, This is a concern as such false-positive results are likely to cause unnecessary patient anxiety in addition to the need for further testing, using valuable resources, to refute the result. In the worst-case scenario, a false-positive result could lead to the inappropriate use of immunosuppressive medication. At present, there is no guidance on which patients are likely to benefit from MSA testing, this guidance will be important if these tests are to be used for diagnostic purposes as the negative and positive predictive values of test results are dependent on the prevalence in the background population. Using optimal methods of MSA detection approximately 60% of adult and juvenile-onset patients with myositis will have an identifiable MSA., This means that at present, unless further MSA are discovered, MSA testing has a relatively low overall sensitivity for myositis, with 40% of patients having no detectable autoantibody. For MSA negative patients, the diagnosis can be more challenging and must be made on clinical grounds supported by other diagnostic tools including muscle enzyme testing, MRI, and muscle biopsy. MSA negative patients are a heterogeneous group and available prognostic information is limited meaning disease complications are difficult to anticipate before they occur.
In contrast to the low sensitivity, MSA are believed to be highly disease specific and therefore a positive result, even in the absence of obvious clinical symptoms, should warrant further investigation, assuming the testing method is considered reliable. The high specificity of MSA can be exploited in key patient populations where an underlying diagnosis of myositis would make a significant difference to the prognosis and treatment. One important such patient group is those presenting with ILD. In future, further refinement of MSA screening may provide additional information; a recent study demonstrated the IgG2 sub-class of anti-TIF1-γ to be particularly associated with malignancy. Indeed, 90% of IIM patients that were anti-TIF1-γ-IgG2 positive had a cancer diagnosis, and this increased to 100% on follow-up. Further work is needed to investigate whether the detection of IgG subclasses enhance the predictive value of MSA. MSA titre is another area for future research which may provide the treating clinician with additional prognostic information. Various small studies have demonstrated a relationship between MSA titer and disease activity measures,,,,, and MSA titer has been suggested as a means of assessing response to treatment in patients with anti-MDA5, however, data have been conflicting.
| Recommendations|| |
The diagnosis of IIM can be made in a patient with compatible clinical features supported by a variety of different investigations. MSA are highly specific and a diagnosis of IIM should be strongly considered in patients with a positive MSA test. A negative MSA test result, however, does not exclude IIM. Clinicians should be aware of the limitations of their chosen testing method.
Muscle biopsy remains a useful diagnostic tool in those patients who are MSA negative and selected MSA-positive patients where the findings could influence clinical management.
MSA may be helpful in identifying those IIM patients presenting with disease apparently confined to the pulmonary system.
The identification of a MSA provides useful prognostic information, particularly regarding the risk of malignancy and development of associated ILD. An appropriate plan for further investigation and monitoring should be created for those patients found to have a MSA strongly associated with malignancy or ILD.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N
Engl J Med 1975;292:344-7.
Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N
Engl J Med 1975;292:403-7.
Tawil R, Griggs RC. Inclusion body myositis. Curr Opinion Rheumatol 2002;14:653-7.
Concha JS, Pena S, Gaffney RG, Patel B, Tarazi M, Kushner CJ, et al
. Developing classification criteria for skin-predominant dermatomyositis: The Delphi process. Br J Dermatol 2020;182:410-7.
Malik A, Hayat G, Kalia JS, Guzman MA. Idiopathic inflammatory myopathies: Clinical approach and management. Front Neurol 2016;7:64.
Cerbelli B, Pisano A, Colafrancesco S, Pignataro MG, Biffoni M, Berni S, et al
. Anti-aminoacyl-tRNA synthetase-related myositis and dermatomyositis: Clues for differential diagnosis on muscle biopsy. Virchows Arch 2018;472:477-87.
Greenberg SA. Inclusion body myositis: Clinical features and pathogenesis. Nat Rev Rheumatol 2019;15:257-72.
Varsani H, Charman SC, Li CK, Marie SK, Amato AA, Banwell B, et al
. Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease. Ann Rheum Dis 2015;74:204-10.
Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al
. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Arthritis Rheumatol 2017;69:2271-82.
Betteridge Z, Tansley S, Shaddick G, Chinoy H, Cooper RG, New RP, et al
. Frequency, mutual exclusivity and clinical associations of myositis autoantibodies in a combined European cohort of idiopathic inflammatory myopathy patients. J Autoimmun 2019;101:48-55.
Tansley SL, Simou S, Shaddick G, Betteridge ZE, Almeida B, Gunawardena H, et al
. Autoantibodies in juvenile-onset myositis: Their diagnostic value and associated clinical phenotype in a large UK cohort. J Autoimmun 2017;84:55-64.
Tansley SL, Betteridge ZE, Simou S, Jacques TS, Pilkington C, Wood M, et al
. Anti-HMGCR autoantibodies in juvenile idiopathic inflammatory myopathies identify a rare but clinically important subset of patients. J Rheumatol 2017;44:488-92.
Trallero-Araguás E, Rodrigo-Pendás JÁ, Selva-O'Callaghan A, Martínez-Gómez X, Bosch X, Labrador-Horrillo M, et al
. Usefulness of anti-p155 autoantibody for diagnosing cancer-associated dermatomyositis: A systematic review and meta-analysis. Arthritis Rheum 2012;64:523-32.
Hoshino K, Muro Y, Sugiura K, Tomita Y, Nakashima R, Mimori T. Anti-MDA5 and anti-TIF1-gamma antibodies have clinical significance for patients with dermatomyositis. Rheumatology (Oxford) 2010;49:1726-33.
Rider LG, Shah M, Mamyrova G, Huber AM, Rice MM, Targoff IN, et al
. The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies. Medicine (Baltimore) 2013;92:223-43.
Oldroyd A, Sergeant JC, New P, McHugh NJ, Betteridge Z, Lamb JA, et al
. The temporal relationship between cancer and adult onset anti-transcriptional intermediary factor 1 antibody-positive dermatomyositis. Rheumatology (Oxford) 2019;58:650-5.
Tansley S, Wedderburn LR. Comparing and contrasting clinical and serological features of juvenile and adult-onset myositis: Implications for pathogenesis and outcomes. Curr Opin Rheumatol 2015;27:601-7.
Cogollo E, Silva MA, Isenberg DA. 186. Why do patients with myositis die? A retrospective analysis of a single centre cohort. Rheumatology 2015;54 Suppl 1:i122.
Aussy A, Fréret M, Gallay L, Bessis D, Vincent T, Jullien D, et al
. The IgG2 isotype of anti-transcription intermediary factor 1γ autoantibodies is a biomarker of cancer and mortality in adult dermatomyositis. Arthritis Rheumatol 2019;71:1360-70.
Hozumi H, Fujisawa T, Nakashima R, Johkoh T, Sumikawa H, Murakami A, et al
. Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease. Respir Med 2016;121:91-9.
Hamaguchi Y, Fujimoto M, Matsushita T, Kaji K, Komura K, Hasegawa M, et al
. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: Heterogeneity within the syndrome. PLoS One 2013;8:e60442.
Mahler M, Miller FW, Fritzler M.J. Idiopathic inflammatory myopathies and the anti-synthetase syndrome: A comprehensive review. Autoimmun Rev 2014;13:367-71.
Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, King TE Jr., Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N
Engl J Med 2012;366:1968-77.
Watanabe K, Handa T, Tanizawa K, Hosono Y, Taguchi Y, Noma S, et al
. Detection of antisynthetase syndrome in patients with idiopathic interstitial pneumonias. Respir Med 2011;105:1238-47.
Fidler L, Doubelt I, Kandel S, Fisher JH, Mittoo S, Shapera S. Screening for myositis antibodies in idiopathic interstitial lung disease. Lung 2019;197:277-84.
Koreeda Y, Higashimoto I, Yamamoto M, Takahashi M, Kaji K, Fujimoto M, et al
. Clinical and pathological findings of interstitial lung disease patients with anti-aminoacyl-tRNA synthetase autoantibodies. Intern Med 2010;49:361-9.
Ghirardello A, Borella E, Beggio M, Franceschini F, Fredi M, Doria A. Myositis autoantibodies and clinical phenotypes. Auto Immun Highlights 2014;5:69-75.
Love LA, Weinberg CR, McConnaughey DR, Oddis CV, Medsger TA Jr, Reveille JD, et al
. Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women. Arthritis Rheum 2009;60:2499-504.
McHugh NJ, Tansley SL. Autoantibodies in myositis. Nat Rev Rheumatol 2018;14:290-302.
Wolstencroft PW, Fiorentino DF. Dermatomyositis clinical and pathological phenotypes associated with myositis-specific autoantibodies. Curr Rheumatol Rep 2018;20:28.
Satoh M, Tanaka S, Ceribelli A, Calise SJ, Chan EK. A comprehensive overview on myositis-specific antibodies: New and old biomarkers in idiopathic inflammatory myopathy. Clin Rev Allergy Immunol 2017;52:1-9.
Sabbagh S, Pinal-Fernandez I, Kishi T, Targoff IN, Miller FW, Rider LG, et al
. Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis. Ann Rheum Dis 2019;78:988-95.
Deakin CT, Yasin SA, Simou S, Arnold KA, Tansley SL, Betteridge ZE, et al
. Muscle biopsy findings in combination with myositis-specific autoantibodies aid prediction of outcomes in juvenile dermatomyositis. Arthritis Rheumatol 2016;68:2806-16.
Vermaak E, Tansley SL, McHugh NJ. The evidence for immunotherapy in dermatomyositis and polymyositis: A systematic review. Clin Rheumatol 2015;34:2089-95.
Tansley SL, Betteridge ZE, Simou S, Jacques TS, Pilkington C, Wood M, et al
. Anti-HMGCR autoantibodies in juvenile idiopathic inflammatory myopathies identify a rare but clinically important subset of patients. J Rheumatol 2017;44:488-92.
Watanabe E, Gono T, Kuwana M, Terai C. Predictive factors for sustained remission with stratification by myositis-specific autoantibodies in adult polymyositis/dermatomyositis. Rheumatology (Oxford) 2020;59:586-93.
Matsuda KM, Yoshizaki A, Kuzumi A, Fukasawa T, Ebata S, Yoshizaki-Ogawa A, et al
. Combined immunosuppressive therapy provides favorable prognosis and increased risk of cytomegalovirus reactivation in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis. J Dermatol 2020;47:483-9.
Motegi SI, Sekiguchi A, Toki S, Kishi C, Endo Y, Yasuda M, et al
. Clinical features and poor prognostic factors of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with rapid progressive interstitial lung disease. Eur J Dermatol 2019;29:511-7.
Abe Y, Matsushita M, Tada K, Yamaji K, Takasaki Y, Tamura N. Clinical characteristics and change in the antibody titres of patients with anti-MDA5 antibody-positive inflammatory myositis. Rheumatology (Oxford) 2017;56:1492-7.
Aggarwal R, Bandos A, Reed AM, Ascherman DP, Barohn RJ, Feldman BM, et al
. Predictors of clinical improvement in rituximab-treated refractory adult and juvenile dermatomyositis and adult polymyositis. Arthritis Rheumatol 2014;66:740-9.
Bellutti Enders F, Bader-Meunier B, Baildam E, Constantin T, Dolezalova P, Feldman BM, et al
. Consensus-based recommendations for the management of juvenile dermatomyositis. Ann Rheum Dis 2017;76:329-40.
Betteridge Z, Gunawardena H, North J, Slinn J, McHugh N. Anti-synthetase syndrome: A new autoantibody to phenylalanyl transfer RNA synthetase (anti-Zo) associated with polymyositis and interstitial pneumonia. Rheumatology (Oxford) 2007;46:1005-8.
Betteridge ZE, Gunawardena H, Chinoy H, North J, Ollier WE, Cooper RG, et al
. Clinical and human leucocyte antigen class II haplotype associations of autoantibodies to small ubiquitin-like modifier enzyme, a dermatomyositis-specific autoantigen target, in UK Caucasian adult-onset myositis. Ann Rheum Dis 2009;68:1621-5.
Espinosa-Ortega F, Holmqvist M, Alexanderson H, Storfors H, Mimori T, Lundberg IE, et al
. Comparison of autoantibody specificities tested by a line blot assay and immunoprecipitation-based algorithm in patients with idiopathic inflammatory myopathies. Ann Rheum Dis 2019;78:858-60.
Tansley SL, Li D, Betteridge ZE, McHugh NJ. The reliability of immunoassays to detect autoantibodies in patients with myositis is dependent on autoantibody specificity. Rheumatology (Oxford). 2020;keaa021. doi: 10.1093/rheumatology/keaa021.
Targoff IN, Mamyrova G, Trieu EP, Perurena O, Koneru B, O'Hanlon TP, et al
. A novel autoantibody to a 155-kd protein is associated with dermatomyositis. Arthritis Rheum 2006;54:3682-9.
Targoff IN, Trieu EP, Miller FW. Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase. J Clin Invest 1993;91:2556-64. doi:10.1172/JCI116493.
Bundell C, Rojana-Udomsart A, Mastaglia F, Hollingsworth P, McLean-Tooke A. Diagnostic performance of a commercial immunoblot assay for myositis antibody testing. Pathology 2016;48:363-6.
Mecoli CA, Albayda J, Tiniakou E, Paik JJ, Zahid U, Danoff SK, et al
. Myositis autoantibodies: A comparison of results from the oklahoma medical research foundation myositis panel to the euroimmun research line blot. Arthritis Rheumatol 2020;72:192-4.
Mahler M, Betteridge Z, Bentow C, Richards M, Seaman A, Chinoy H, et al
. Comparison of three immunoassays for the detection of myositis specific antibodies. Front Immunol 2019;10:848.
Gono T, Sato S, Kawaguchi Y, Kuwana M, Hanaoka M, Katsumata Y, et al
. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford) 2012;51:1563-70.
Koga T, Fujikawa K, Horai Y, Okada A, Kawashiri SY, Iwamoto N, et al
. The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology (Oxford) 2012;51:1278-84.
Muro Y, Sugiura K, Akiyama M. Limitations of a single-point evaluation of anti-MDA5 antibody, ferritin, and IL-18 in predicting the prognosis of interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Clin Rheumatol 2013;32:395-8.
Muro Y, Sugiura K, Hoshino K, Akiyama M. Disappearance of anti-MDA-5 autoantibodies in clinically amyopathic DM/interstitial lung disease during disease remission. Rheumatology (Oxford) 2012;51:800-4.
Stone KB, Oddis CV, Fertig N, Katsumata Y, Lucas M, Vogt M, et al
. Anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy. Arthritis Rheum 2007;56:3125-31.