Elevated serum levels of soluble interleukin‐2 receptor in juvenile dermatomyositis

Kobayashi, Ichiro; Ono, Shun; Kawamura, Nobuaki; Okano, Motohiko; Kobayashi, Kunihiko

doi:10.1046/j.1442-200x.2001.01367.x

Cited by 18 publications

(8 citation statements)

References 11 publications

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“…Twenty cytokines were up-regulated in our DM or PM patient cohort, many of which have been reported to be overexpressed in muscle tissue sections of IIMs, such as IL-18, monocyte chemoattractant protein 1 (MCP-1), and B-cell activating factor (BAFF) [15, 16]. Several soluble cytokine receptors and adhesion molecules [IL-2RA, TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule 1 (VCAM-1)] demonstrated elevated levels in DM or PM patients, which was consistent with previous reports [17–19]. Our results also indicated overexpression of ANGPT2 and soluble B2M, which has been reported in SLE and SSc, but not IIMs [20–22].…”

Section: Resultssupporting

confidence: 89%

Suppression of soluble T cell-associated proteins by an anti-interferon- monoclonal antibody in adult patients with dermatomyositis or polymyositis

et al. 2013

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Objective. The aim of this study was to identify serum markers that are modulated by an investigational anti-IFN-α mAb, sifalimumab, in adult DM or PM patients.Methods. In a phase 1b clinical trial, sera were collected from a total of 48 DM or PM adult patients receiving either placebo for 3 months or sifalimumab for 6 months. Samples were tested for 128 selected proteins using a multiplex luminex immunoassay. Muscle biopsies from selected patients were stained for T cell infiltration using an anti-CD3 antibody.Results. A robust overexpression of multiple serum proteins in DM or PM patients was observed, particularly in patients with an elevated baseline type I IFN gene signature in the blood or muscle. Neutralization of the type I IFN gene signature by sifalimumab resulted in coordinated suppression of T cell-related proteins such as soluble IL-2RA, TNF receptor 2 (TNFR2) and IL-18. Muscle biopsies from two patients with the highest serum protein suppression were selected and found to have a pronounced reduction of muscle T cell infiltration. Down-regulation of IL-2RA correlated with favourable manual muscle test 8 (MMT-8) alterations in sifalimumab-dosed patients.Conclusion. A reduced level of multiple T cell-associated proteins after sifalimumab but not placebo administration suggests a suppressive effect of blocking type I IFN signalling on T cell activation and chemoattraction that may lead to a reduction of T cell infiltration in the muscle of myositis patients. Further, soluble IL-2RA changes from baseline may serve as a responsive and/or predictive marker for type I IFN-targeted therapy in adult DM or PM patients.

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Section: Resultssupporting

confidence: 89%

Suppression of soluble T cell-associated proteins by an anti-interferon- monoclonal antibody in adult patients with dermatomyositis or polymyositis

et al. 2013

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“…Von Willebrand factor and fibrin degradation product reflect activation and damage of vascular endothelial cells [26][27][28]. Serum levels of ferritin, neopterin and soluble interleukin-2 receptor also correlate with disease activity but are not specific to JDM [29][30][31][32][33]. Myositis-specific antibodies are mentioned in the next section.…”

Section: Laboratory Examinationmentioning

confidence: 99%

Clinical practice guidance for juvenile dermatomyositis (JDM) 2018-Update

Kobayashi

Akioka

Kobayashi

et al. 2020

Modern Rheumatology

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Juvenile dermatomyositis is the most common type of juvenile idiopathic inflammatory myopathy mainly affecting the skin and proximal muscles. We have published the Japanese version of 'Clinical practice guidance for juvenile dermatomyositis (JDM) 2018 'consisting of a review of articles in the field and evidence-informed consensus-based experts' opinion on the treatment strategy in collaboration with The Pediatric Rheumatology Association of Japan and The Japan College of Rheumatology under the financial support by 'Research on rare and intractable diseases, Health and Labor Sciences Research Grants'. This article is a digest version of the Japanese guidance.

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“…In the first study identifying serum neopterin as a biomarker for JDM, neopterin levels correlated strongly with muscle strength impairment in 15 JDM patients ( r s = 0.68) (96). Elevated serum neopterin levels at diagnosis compared to remission were confirmed in an independent cohort (95). In a juvenile myositis validation cohort, plasma neopterin ( n = 13), and quinolonic acid ( n = 24), however, did not correlate with myositis disease activity measures (97).…”

Section: Monitoring Of Disease Activity and Tissue Involvementmentioning

confidence: 76%

Systemic and Tissue Inflammation in Juvenile Dermatomyositis: From Pathogenesis to the Quest for Monitoring Tools

et al. 2018

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Juvenile Dermatomyositis (JDM) is a systemic immune-mediated disease of childhood, characterized by muscle weakness, and a typical skin rash. Other organ systems and tissues such as the lungs, heart, and intestines can be involved, but may be under-evaluated. The inflammatory process in JDM is characterized by an interferon signature and infiltration of immune cells such as T cells and plasmacytoid dendritic cells into the affected tissues. Vasculopathy due to loss and dysfunction of endothelial cells as a result of the inflammation is thought to underlie the symptoms in most organs and tissues. JDM is a heterogeneous disease, and several disease phenotypes, each with a varying combination of affected tissues and organs, are linked to the presence of myositis autoantibodies. These autoantibodies have therefore been extensively studied as biomarkers for the disease phenotype and its associated prognosis. Next to identifying the JDM phenotype, monitoring of disease activity and disease-inflicted damage not only in muscle and skin, but also in other organs and tissues, is an important part of clinical follow-up, as these are key determinants for the long-term outcomes of patients. Various monitoring tools are currently available, among which clinical assessment, histopathological investigation of muscle and skin biopsies, and laboratory testing of blood for specific biomarkers. These investigations also give novel insights into the underlying immunological processes that drive inflammation in JDM and suggest a strong link between the interferon signature and vasculopathy. New tools are being developed in the quest for minimally invasive, but sensitive and specific diagnostic methods that correlate well with clinical symptoms or reflect local, low-grade inflammation. In this review we will discuss the types of (extra)muscular tissue inflammation in JDM and their relation to vasculopathic changes, critically assess the available diagnostic methods including myositis autoantibodies and newly identified biomarkers, and reflect on the immunopathogenic implications of identified markers.

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Elevated serum levels of soluble interleukin‐2 receptor in juvenile dermatomyositis

Cited by 18 publications

References 11 publications

Suppression of soluble T cell-associated proteins by an anti-interferon- monoclonal antibody in adult patients with dermatomyositis or polymyositis

Suppression of soluble T cell-associated proteins by an anti-interferon- monoclonal antibody in adult patients with dermatomyositis or polymyositis

Clinical practice guidance for juvenile dermatomyositis (JDM) 2018-Update

Systemic and Tissue Inflammation in Juvenile Dermatomyositis: From Pathogenesis to the Quest for Monitoring Tools

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