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Resource and Technical AdvanceIn-Press PreviewDermatologyInflammation Open Access | 10.1172/jci.insight.179875

Tape strip expression profiling of juvenile dermatomyositis skin reveals mitochondrial dysfunction contributing to disease endotype

Jessica L. Turnier,1 Sarah M.H. Vandenbergen,1 Madison E. McClune,1 Christine Goudsmit,1 Sophia Matossian,1 Meredith Riebschleger,1 Nadine Saad,1 Jacqueline A. Madison,1 Smriti Mohan,1 Johann E. Gudjonsson,2 Lam C. Tsoi,3 Celine C. Berthier,4 and J. Michelle Kahlenberg2

1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

Find articles by Berthier, C. in: JCI | PubMed | Google Scholar |

1Division of Pediatric Rheumatology, University of Michigan, Ann Arbor, United States of America

2Department of Pediatrics, Division of Rheumatology, University of Michigan, Ann Arbor, United States of America

3Department of Internal Medicine, Department of Dermatology, University of Michigan, Ann Arbor, United States of America

4Division of Nephrology, University of Michigan, Ann Arbor, United States of America

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Published March 13, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.179875.
Copyright © 2025, Turnier et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published March 13, 2025 - Version history
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Abstract

Skin inflammation in juvenile dermatomyositis (JDM) can signal disease onset or flare, and the persistence of cutaneous disease can prevent complete disease remission. The non-invasive study of cutaneous expression signatures through tape stripping (TS) holds the potential to reveal mechanisms underlying disease heterogeneity and organ-specific inflammation. The objectives of this study were to 1) define TS expression signatures in lesional and non-lesional JDM skin, 2) analyze TS signatures to identify JDM disease endotypes and 3) compare TS and blood signatures. While JDM lesional skin demonstrated interferon signaling as the top upregulated pathway, non-lesional skin uniquely highlighted pathways involved in metabolism, angiogenesis and calcium signaling. Both lesional and non-lesional skin shared inflammasome pathway dysregulation. Using unsupervised clustering of skin expression data, we identified a treatment-refractory JDM subgroup distinguished by upregulation of genes associated with mitochondrial dysfunction. The treatment-refractory JDM subgroup also demonstrated higher interferon, angiogenesis and innate immune expression scores in skin and blood, although scores were more pronounced in skin as compared to blood. Tape-stripping expression signatures in JDM provided insight into disease mechanisms and molecular subgroups. Skin, as compared to blood, transcriptional profiles served as more sensitive markers to classify disease subgroups and identify candidate treatment targets.

Graphical Abstract
graphical abstract
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Version history
  • Version 1 (March 13, 2025): In-Press Preview
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