Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease

Nakashima, Ran; Hosono, Yuji; Mimori, Tsuneyo

doi:10.1177/0961203316651748

Cited by 99 publications

(85 citation statements)

References 76 publications

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“…MSAs are detected in 45-85% of adult IIM patients and in 50-70% of juvenile IIM (JIIM) patients [1][2][3][4][5][6][7][8]. In adult patients, anti-ARSs are most frequently detected (20-40% of IIM cases) followed by anti-MDA5 (8-20%), anti-SRP (3-10%), anti-TIF1-c (5-7%), anti-Mi-2 (3-8%) and anti-NXP2 (5-8%) [2,9]. The most frequent MSAs in JIIM are anti-NXP2 (15-23%), anti-TIF1-c (15-35%) and anti-MDA5 (7-28%); in contrast, anti-ARSs are relatively rare (2-8%) [5].…”

Section: Myositis-specific Autoantibodiesmentioning

confidence: 99%

“…Anti-ARS-positive patients develop common clinical manifestations, characterized by myositis, ILD, arthritis, fever, Raynaud's phenomenon and mechanic's hand, which is called 'anti-synthetase syndrome (ASS)' [22]. Anti-ARSs have a strong association with ILD because 70-95% of anti-ARS-positive patients [21,23,24] have ILD and 40-55% of PM/DM patients with ILD are positive for anti-ARSs [2,25]. Anti-ARS-positive ILD tends to be diagnosed at the same time or even before the development of myositis [22].…”

Section: Anti-arsmentioning

confidence: 99%

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Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

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To date, increasing numbers of myositis-specific autoantibodies (MSAs) have been reported and their clinical significance has been elucidated. Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma-differentiation associated gene 5 (MDA5) are strongly associated with interstitial lung disease (ILD); however, the clinical course of ILD is different depending on which autoantibody is present. Anti-ARS is associated with chronic and repetitive ILD and anti-MDA5 is associated with rapidly progressive ILD. Anti-MDA5, anti-transcriptional intermediary factor (TIF) 1-c, anti-nuclear matrix protein (NXP) 2 and anti-Mi-2 antibodies are dermatomyositis specific. Anti-TIF1-c and anti-NXP-2 antibodies are associated with malignancy, and anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies are associated with immune-mediated necrotizing myopathy (IMNM). Prognosis is also different among MSA-positive patient groups. Thus, MSAs are of great use for predicting disease course, prognosis, and determining therapeutic strategy as well as the diagnosis of idiopathic inflammatory myopathy (IIM) patients. Investigation of the pathogenic role of MSAs and their corresponding autoantigens will help us to understand the pathophysiology of IIM and identify new therapeutic targets. ARTICLE HISTORY

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Section: Myositis-specific Autoantibodiesmentioning

confidence: 99%

Section: Anti-arsmentioning

confidence: 99%

Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

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“…Recently, some case reports have suggested that a combined immunosuppressive therapy might be efficacious; this type of therapy includes high‐dose GCs, calcineurin inhibitors (CNIs), and intravenous cyclophosphamide (IV CYC), which are administered beginning in the early phase of rapidly progressive ILD with DM/CADM . In addition, we have observed the effectiveness of such combination therapy in the early stage of rapidly progressive ILD in Japanese patients with anti–MDA‐5–positive DM/CADM, compared to those receiving step‐up therapy (75% versus 29%) at our hospital . However, there has not been a prospective trial examining the efficacy and safety of this combination therapy.…”

Section: Introductionmentioning

confidence: 98%

Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High‐Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis

Tsuji

Nakashima

Hosono

et al. 2020

Arthritis & Rheumatology

238

168

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Objective Interstitial lung disease (ILD) accompanied by anti–melanoma differentiation–associated gene 5 (anti–MDA‐5)–positive dermatomyositis (DM) is often rapidly progressive and associated with poor prognosis. Because there is no established treatment, we undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti–MDA‐5–positive DM patients with ILD. Methods Adult Japanese patients with new‐onset anti–MDA‐5–positive DM with ILD (n = 29) were enrolled at multiple study centers from 2014 to 2017. They were treated with a regimen of high‐dose glucocorticoids (GCs), tacrolimus, and intravenous cyclophosphamide (IV CYC). Plasmapheresis was used if a patient's condition worsened after the regimen started. The primary end point was 6‐month survival, which was compared between this group of patients and a historical control group (n = 15) consisting of anti–MDA‐5–positive DM patients with ILD who received step‐up treatment (high‐dose GC and stepwise addition of immunosuppressant). Secondary end points were 12‐month survival rate, adverse events, and changes in laboratory data. Results The combined immunosuppressive regimen group showed significantly higher 6‐month survival rates than the step‐up treatment group (89% versus 33%; P < 0.0001). Over a period of 52 weeks, improvements in anti–MDA‐5 titers, serum ferritin levels, vital capacity, and chest high‐resolution computed tomography scores were observed. The combined immunosuppressive regimen group received IV CYC nearly 20 days earlier with shorter intervals and tended to receive plasmapheresis more often than patients undergoing step‐up treatment. Cytomegalovirus reactivation was frequently observed over 52 weeks. Conclusion A combined immunosuppressive regimen is effective for anti–MDA‐5–positive DM patients with ILD. Plasmapheresis can be used for additional effect in intractable disease. Patients should be carefully monitored for opportunistic infections during treatment.

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“…Anti-MDA5 positivity was reported to be associated with a specific presentation of CADM featuring painful ulcerations over extensor surfaces and nailfolds, hyperferritinemia, and frequent treatment-resistant, rapidly progressive ILD associated with poor prognosis 3, 13. Interestingly, MDA5 protein functions as an intracellular pathogen sensor involved in the recognition and mounting of immune response to viral RNA 3, 4. Hence, there could be an association between CADM and viral infections perhaps explaining the incidence of ILD.…”

Section: Discussionmentioning

confidence: 99%

“…Clinically amyopathic DM (CADM) accounts for approximately 20% of all cases and is diagnosed based on the presence of pathognomonic cutaneous involvement 2, 3. Antibody against melanoma differentiation–associated protein 5 (MDA5) was recently found to be specific for CADM associated with rapidly progressive interstitial lung disease (ILD) 4 . To our knowledge, there are no other cases of MDA5-positive CADM in an HIV-positive patient.…”

Section: Introductionmentioning

confidence: 99%