Overview

Juvenile myositis (JM) is a rare, complex, multi-system condition in which inflammation of the muscles results in weakness as well as a characteristic skin rash in cases of juvenile dermatomyositis (JDM). The exact cause or pathogenesis of JM is not well understood but it is thought to result from a combination of multiple genetic and environmental risk factors. Treatment is generally empiric with prolonged and high-doses of immunosuppression medications including glucocorticoids, which carry significant adverse effects.  

Sixty to seventy percent of patients have a chronic disease course, and some are unable to achieve remission with currently available medications. In the long term, the disease often causes damage such as calcinosis and impaired function. Better markers to help monitor and predict the disease course and guide therapy are needed, as well as more targeted therapy options with better efficacy and fewer side effects.

Our group studies dysregulated gene and protein expression from patients with JM to better understand dysregulated biology and the pathogenesis of the disease. An interferon response signature has been demonstrated in peripheral blood, muscle, and skin in dermatomyositis. To better understand the role of interferon in JDM, we have compared the peripheral interferon signature, or score, in JDM to autoinflammatory Mendelian interferonopathies (PMID 32252809, PMID 29638206). Janus kinase (JAK) inhibitors can target this interferon signaling pathway. Given the interferon signature, which is well described in JDM, and previous use of JAK inhibitors in Mendelian interferonopathies, we studied the use of baricitinib (a JAK inhibitor) in refractory JDM, demonstrating proof of concept in pharmacodynamic studies as well as clinical efficacy (PMID 32843325).

These studies have highlighted how we have looked at particular pathways and utilized Mendelian disease to better understand pathogenesis and guide the selection of targeted therapy.

Research Focus

Our collaborative group studies are focused on better understanding the etiology and mechanisms of disease in juvenile myositis in order to optimize management and treatment. We are focused on:

  • Elucidating the immunopathogenesis of the disease and potential predictors of treatment response by the discovery of novel biomarkers through transcriptomic, proteomic, and/or immunophenotyping analyses.
  • Investigating novel treatments in small clinical trials to establish more targeted therapy with the goal of identifying safe treatments with greater efficacy and fewer side effects.

Ongoing Studies

The following studies are currently active. Further details are available following the links to the respective pages on the clinicaltrials.gov web site.

RECRUITING

Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases Including Juvenile Dermatomyositis

ClinicalTrials.gov Identifier: NCT00059748 [03-AR-0173]

Autoinflammatory multisystem diseases are a group of diseases that are characterized by recurrent episodes of systemic inflammation as well as organ specific inflammation that can involve the skin, eyes, joints, bones, serosal surfaces, inner ear, and brain. In this research protocol we seek to comprehensively evaluate affected patients clinically, genetically, immunologically, and endocrinologically. In addition we intend to evaluate longterm outcomes and biomarkers over the time of observations. Eligibility for ongoing and planned treatment protocols will be determined by screening patients in this protocol. We plan to evaluate patients on a consultative basis for other autoinflammatory diseases for possible enrollment into this study.

Core Research Facilities

Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

Staff

Image
Members of Hanna Kim's Lab, 2021
Assistant Clinical Investigator
Postbaccalaureate Fellow
Postbaccalaureate Fellow

Image & Media Gallery

Scientific Publications

Selected Recent Publications

Updates on Juvenile Dermatomyositis from the Last Decade: Classification to Outcomes.

Kim H, Huber AM, Kim S
Rheum Dis Clin North Am.
2021 Nov;
47(4).
doi: 10.1016/j.rdc.2021.07.003
PMID: 34635298

Updates on interferon in juvenile dermatomyositis: pathogenesis and therapy.

Kim H
Curr Opin Rheumatol.
2021 Sep 1;
33(5).
doi: 10.1097/BOR.0000000000000816
PMID: 34230439

Janus kinase (JAK) inhibition with baricitinib in refractory juvenile dermatomyositis.

Kim H, Dill S, O'Brien M, Vian L, Li X, Manukyan M, Jain M, Adeojo LW, George J, Perez M, Grom AA, Sutter M, Feldman BM, Yao L, Millwood M, Brundidge A, Pichard DC, Cowen EW, Shi Y, Lu S, Tsai WL, Gadina M, Rider LG, Colbert RA
Ann Rheum Dis.
2020 Aug 25;
pii: annrheumdis-2020-218690. doi: 10.1136/annrheumdis-2020-218690
PMID: 32843325

Expression of interferon-regulated genes in juvenile dermatomyositis versus Mendelian autoinflammatory interferonopathies.

Kim H, Gunter-Rahman F, McGrath JA, Lee E, de Jesus AA, Targoff IN, Huang Y, O'Hanlon TP, Tsai WL, Gadina M, Miller FW, Goldbach-Mansky R, Rider LG
Arthritis Res Ther.
2020 Apr 6;
22(1).
doi: 10.1186/s13075-020-02160-9
PMID: 32252809

Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.

de Jesus AA, Hou Y, Brooks S, Malle L, Biancotto A, Huang Y, Calvo KR, Marrero B, Moir S, Oler AJ, Deng Z, Montealegre Sanchez GA, Ahmed A, Allenspach E, Arabshahi B, Behrens E, Benseler S, Bezrodnik L, Bout-Tabaku S, Brescia AC, Brown D, Burnham JM, Caldirola MS, Carrasco R, Chan AY, Cimaz R, Dancey P, Dare J, DeGuzman M, Dimitriades V, Ferguson I, Ferguson P, Finn L, Gattorno M, Grom AA, Hanson EP, Hashkes PJ, Hedrich CM, Herzog R, Horneff G, Jerath R, Kessler E, Kim H, Kingsbury DJ, Laxer RM, Lee PY, Lee-Kirsch MA, Lewandowski L, Li S, Lilleby V, Mammadova V, Moorthy LN, Nasrullayeva G, O'Neil KM, Onel K, Ozen S, Pan N, Pillet P, Piotto DG, Punaro MG, Reiff A, Reinhardt A, Rider LG, Rivas-Chacon R, Ronis T, Rösen-Wolff A, Roth J, Ruth NM, Rygg M, Schmeling H, Schulert G, Scott C, Seminario G, Shulman A, Sivaraman V, Son MB, Stepanovskiy Y, Stringer E, Taber S, Terreri MT, Tifft C, Torgerson T, Tosi L, Van Royen-Kerkhof A, Wampler Muskardin T, Canna SW, Goldbach-Mansky R
J Clin Invest.
2020 Apr 1;
130(4).
doi: 10.1172/JCI129301
PMID: 31874111

Treatment of anti-MDA5 autoantibody-positive juvenile dermatomyositis using tofacitinib.

Sabbagh S, Almeida de Jesus A, Hwang S, Kuehn HS, Kim H, Jung L, Carrasco R, Rosenzweig S, Goldbach-Mansky R, Rider LG
Brain.
2019 Nov 1;
142(11).
doi: 10.1093/brain/awz293
PMID: 31603187

Pharmacokinetics, Pharmacodynamics, and Proposed Dosing of the Oral JAK1 and JAK2 Inhibitor Baricitinib in Pediatric and Young Adult CANDLE and SAVI Patients.

Kim H, Brooks KM, Tang CC, Wakim P, Blake M, Brooks SR, Montealegre Sanchez GA, de Jesus AA, Huang Y, Tsai WL, Gadina M, Prakash A, Janes JM, Zhang X, Macias WL, Kumar P, Goldbach-Mansky R
Clin Pharmacol Ther.
2018 Aug;
104(2).
doi: 10.1002/cpt.936
PMID: 29134648

JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies.

Sanchez GAM, Reinhardt A, Ramsey S, Wittkowski H, Hashkes PJ, Berkun Y, Schalm S, Murias S, Dare JA, Brown D, Stone DL, Gao L, Klausmeier T, Foell D, de Jesus AA, Chapelle DC, Kim H, Dill S, Colbert RA, Failla L, Kost B, O'Brien M, Reynolds JC, Folio LR, Calvo KR, Paul SM, Weir N, Brofferio A, Soldatos A, Biancotto A, Cowen EW, Digiovanna JJ, Gadina M, Lipton AJ, Hadigan C, Holland SM, Fontana J, Alawad AS, Brown RJ, Rother KI, Heller T, Brooks KM, Kumar P, Brooks SR, Waldman M, Singh HK, Nickeleit V, Silk M, Prakash A, Janes JM, Ozen S, Wakim PG, Brogan PA, Macias WL, Goldbach-Mansky R
J Clin Invest.
2018 Jul 2;
128(7).
doi: 10.1172/JCI98814
PMID: 29649002

Development of a Validated Interferon Score Using NanoString Technology.

Kim H, de Jesus AA, Brooks SR, Liu Y, Huang Y, VanTries R, Montealegre Sanchez GA, Rotman Y, Gadina M, Goldbach-Mansky R
J Interferon Cytokine Res.
2018 Apr;
38(4).
doi: 10.1089/jir.2017.0127
PMID: 29638206

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

Spencer CH, Rouster-Stevens K, Gewanter H, Syverson G, Modica R, Schmidt K, Emery H, Wallace C, Grevich S, Nanda K, Zhao YD, Shenoi S, Tarvin S, Hong S, Lindsley C, Weiss JE, Passo M, Ede K, Brown A, Ardalan K, Bernal W, Stoll ML, Lang B, Carrasco R, Agaiar C, Feller L, Bukulmez H, Vehe R, Kim H, Schmeling H, Gerstbacher D, Hoeltzel M, Eberhard B, Sundel R, Kim S, Huber AM, Patwardhan A, Pediatric Rheumatologist Collaborators.
Pediatr Rheumatol Online J.
2017 Jun 13;
15(1).
doi: 10.1186/s12969-017-0174-0
PMID: 28610606

Insights from Mendelian Interferonopathies: Comparison of CANDLE, SAVI with AGS, Monogenic Lupus.

Kim H, Sanchez GA, Goldbach-Mansky R
J Mol Med (Berl).
2016 Oct;
94(10).

Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production.

Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q, Montealegre G, Biancotto A, Reinhardt A, de Jesus AA, Pelletier M, Tsai WL, Remmers EF, Kardava L, Hill S, Kim H, Lachmann HJ, Megarbane A, Chae JJ, Brady J, Castillo RD, Brown D, Casano AV, Gao L, Chapelle D, Huang Y, Stone D, Chen Y, Sotzny F, Lee CC, Kastner DL, Torrelo A, Zlotogorski A, Moir S, Gadina M, McCoy P, Wesley R, Rother KI, Hildebrand PW, Brogan P, Krüger E, Aksentijevich I, Goldbach-Mansky R
J Clin Invest.
2016 Feb;
126(2).
doi: 10.1172/JCI86020
PMID: 26829627

Activated STING in a vascular and pulmonary syndrome.

Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Sanchez GAM, Tenbrock K, Wittkowski H, Jones OY, Kuehn HS, Lee CR, DiMattia MA, Cowen EW, Gonzalez B, Palmer I, DiGiovanna JJ, Biancotto A, Kim H, Tsai WL, Trier AM, Huang Y, Stone DL, Hill S, Kim HJ, St Hilaire C, Gurprasad S, Plass N, Chapelle D, Horkayne-Szakaly I, Foell D, Barysenka A, Candotti F, Holland SM, Hughes JD, Mehmet H, Issekutz AC, Raffeld M, McElwee J, Fontana JR, Minniti CP, Moir S, Kastner DL, Gadina M, Steven AC, Wingfield PT, Brooks SR, Rosenzweig SD, Fleisher TA, Deng Z, Boehm M, Paller AS, Goldbach-Mansky R
N Engl J Med.
2014 Aug 7;
371(6).
doi: 10.1056/NEJMoa1312625
PMID: 25029335

News & Highlights

NIAMS-Related Article | March 4, 2022

What Our Proteins Can Tell Us About Autoimmune Diseases

Adeline Chin, a postbaccalaureate research fellow, is searching for proteins present at abnormally high or low levels in the blood of kids with a rare autoimmune illness.