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Juvenile Dermatomyositis: Advances in basic research, translational studies and clinical care

Virtual Symposium
March 12th, 10:00 am EDT

3 CME Credits Available

In support of improving patient care, the Duke University Health System Department of Clinical Education and Professional Development is accredited by the American Nurses Credentialing Center (ANCC), the Accreditation Council for Pharmacy Education (ACPE), and the Accreditation Council for Continuing Medical Education (ACCME), to provide continuing education for the health care team.

Duke Health

 

Joint Accreditation Interprofessional Continuing Education


Physician Credit: Duke University Health System Department of Clinical Education and Professional Development designates this activity for a maximum of 3 AMA PRA Category 1 Credit(s)™. Physicians should claim only credit commensurate with the extent of their participation in the activity.

Activity ID: LA_JA_20220312 2022 Juvenile Dermatomyositis: Advances in Basic Research, Translational Studies, and Clinical Care

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Commercial support received from Janssen Pharmaceutical Companies of Johnson & Johnson.
Co-hosted by Cure JM Foundation.


Agenda:

Session 1  
10:00 - 10:10

Opening comments and introduction

Kristine Alderfer (President Cure JM Foundation),
Andrew Heaton PhD  (CSO, Cure JM Foundation)

10:10 - 10:35

Keynote Speaker

Brian Feldman, MD (Hospital for SickKids Toronto CA)

Lifestyle changes as treatment for childhood myositis
Dr. Feldman will present research and conceptual work supporting the role of exercise, diet, supplements, and sleep as adjunctive therapies for children with myositis.

10:35 - 11:00

Kaveh Ardalan, MD (Duke University)
Andrea Knight, MD (Hospital for SickKids Toronto, CA)

Impact of Juvenile Myositis on Mental Health
Recent studies suggest that children with a variety of rheumatologic conditions, including JM, frequently experience significant emotional distress that can sometimes persist even when the disease itself is in remission.  Accessing high quality treatment for mental health needs remains challenging for many families.  In this talk, Drs. Kaveh Ardalan and Andrea Knight will give an overview of what has been learned about the mental health of impact in JM in recent years and ongoing work in the pediatric rheumatology to set an agenda for addressing this important aspect of patient care.

11:00 - 11:25

Meredyth Wilkinson, PhD (UCL/ GOSH, UK)

A new therapeutic target: oxidised mitochondrial DNA induces an interferon response in Juvenile Dermatomyositis
Immunologically, JDM is characterized by a strong interferon (IFN) type I signature within peripheral blood mononuclear cells (PBMC) compared to age-matched healthy controls (CHC). Dr. Wilkinson’s study aimed at identifying dysregulated pathways up-stream of IFN type 1 to address the unmet need for novel targeted therapies in this devastating childhood condition. Dr. Wilkinson will present results that have identified  mitochondrial dysfunction as a new pathway involved in the pathology of JDM and a mechanism of oxidised mitochondrial DNA induced IFN type 1 as a potential novel therapeutic target in JDM.

11:25 - 11:50

Rebecca Sadun, MD (Duke University)

Mind the Gap: pearls for helping JDM patients succeed in transition and transfer to adult care
Dr. Sadun is Program Director for the Pediatric Rheumatology Fellowship and directs a Young Adult Rheumatology Clinic that helps patients transfer to adult care.  Dr. Sadun will present her experience and a curriculum she developed aimed at teaching rheumatology fellows the skills needed to help young adult patients transition and transfer from pediatric to adult rheumatology care. 

Session 2  
Noon - 12:25

Keynote Speaker

Ann Reed, MD (Duke University)

Demystifying the value of autoantibodies in juvenile myositis
Juvenile myositis is a rare and heterogeneous disease that makes identifying unified treatment and outcomes difficult. Myositis specific autoantibodies have been described in both juvenile and adult patients with myositis and have been of help in more homogeneous patient groups based on outcomes, clinical features and in the future outcomes to therapy by allowing us to look at patients with similar phenotypes. 

Myositis specific autoantibodies continue to be discovered and have expanded in number and also our understanding of the disease subsets in the past few decades. This has also led to identification of some of the related antigens in tissue of patients with myositis and advancing our knowledge of the field. This presentation will share with you the history of myositis specific autoantibodies, learn about the clinical phenotypes associated with the antibody and explore what we know about outcome in the subsets.
12:25 - 12:50

Jessica Neely, MD (UCSF)

Immunophenotypes associated with JDM disease activity identified through single cell sequencing
JDM has been associated with a strong interferon (IFN) signature identified through bulk RNA sequencing methods, however, the primary immune cell source of this signature and the immune cell types associated with disease activity are not well understood.  Using single-cell RNA and protein sequencing, we used a systems biologist approach to simultaneously interrogate all immune cell types in treatment-naïve JDM.  Dr. Neely will present analysis of monocytes that express the highest IFN signature of all peripheral blood cell types and are highly skewed toward an inflammatory and antigen-presenting phenotype.  Dr Neely will also preset data on identification a population of transitional naïve B cells characterized by a distinct proteomic and transcriptomic signature that was expanded in the treatment-naïve state.  Further data identified that the IFN signature in cytotoxic cell types, CD8+ T cells and CD56dim cells, best correlated with disease activity.   This data adds to the knowledge of the immune dysregulation present in JDM.   Increasing our understanding of the immunophenotypes associated with JDM can lead to the development of personalized treatment strategies.

12:50 - 1:15

Jessica Turnier, MD (University of Michigan)

Defining skin disease mechanisms in juvenile myositis to improve treatment
Dr. Turnier will present data on JDM skin disease focused on defining cutaneous gene expression signatures and immune cell subpopulations through harnessing transcriptomics and imaging mass cytometry of existing formalin-fixed, paraffin-embedded skin biopsy samples. The study utilized the direct comparison of molecular disease signatures with childhood-onset systemic lupus erythematosus (cSLE) to identify disease-specific mechanisms and treatment targets.  Dr. Turnier has identified a shared type I interferon signature in JDM and cSLE skin, although cSLE overall demonstrated a higher inflammatory signature. JDM as compared to cSLE skin had only 28 unique differentially expressed genes, including FBLN2, CHKA and SLURP1, which were used to generate a JDM-specific skin score. JDM patients were noted to have a predominant innate immune signature in skin, with CD14+ macrophages noted as the most populous immune cell type.

1:15 - 1:40

Christian Lood, PhD (University of Washington)

Mitochondrial calcification as a novel mechanism in calcinosis pathogenesis
Calcinosis, accumulation of calcium phosphate crystals in soft tissues, is one of the debilitating manifestations of juvenile dermatomyositis (JDM). Mechanistic understanding of calcinosis in JDM remains poorly understood, thus impeding therapeutic strategies. Prior studies in mice suggested a role of mitochondria in calcinosis pathogenesis. Dr. Lood will detail the novel observation of intramitochondrial calcification in muscle biopsies of JDM children with calcinosis. Mechanistically, inflammatory cytokines, including interferon alpha, promote mitochondrial reactive oxygen species enhancing uptake of calcium into the mitochondria, resulting in formation of intramitochondrial deposits of calcium phosphate crystals, e.g. hydroxyapatite. The crystals caused mitochondrial damage, resulting in release of mitochondrial components, including its DNA, into the cytosol, signaling induction of type I interferons through the cGAS/STING DNA-sensing pathway, as well as IL-1B through the inflammasome pathway. Calcified mitochondria were not contained solely within the damaged muscle cell, but could also be seen to be extruded into the extracellular space both in vitro and in vivo using electron microscopy. Consistently, elevated levels of extracellular mitochondrial components, including mtDNA, were found in circulation of JDM patients, in particular in those with calcinosis.

1:40 - 1:50

Closing remarks

Jeffrey Dvergsten, MD (Duke University)

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