Overview

The Muscle Disease Section focuses its research on myositis, a rare family of autoimmune diseases in which the body's immune system attacks healthy muscle tissue, causing inflammation, weakness, fatigue, and pain in skeletal muscles. Problems that affect the skin, lungs, and joints often accompany myositis. 

Research Focus:

  • Dermatomyositis, which can include a skin rash.
  • The anti-synthetase syndrome, which can include a rash, lung disease, and arthritis.
  • Inclusion body myositis, which typically affects the muscles of older adults. 
  • Immune-mediated necrotizing myopathy, which can cause especially severe weakness in children and adults alike.

Lab Goals: 

  • Define the different subtypes of autoimmune muscle disease based on muscle histology, autoantibodies, and other biomarkers.
  • Describe the role of myositis autoantibodies in the pathogenesis of myositis. 
  • Develop animal models of myositis that are relevant to human diseases.
  • Understand how environmental exposures, including medications such as statins and cancer immunotherapies, can trigger autoimmune muscle disease. 
  • Use novel therapeutic strategies to treat myositis patients at the NIH Clinical Center.

In 2007, while on the faculty at Johns Hopkins, Dr. Mammen co-founded the Johns Hopkins Myositis Center. This group discovered a form of immune-mediated necrotizing myopathy triggered by statins, a medication used to lower cholesterol concentrations (Arthritis Rheum 63:713–721, 2011). This disease occurs in approximately 1 in 50,000 Black and white Americans exposed to statins. However, working with colleagues in New Mexico, they found that around 1 in 300 members of the Navajo Nation may develop this form of myositis if exposed to statins (Arthritis Rheum 2022; DOI:10.1002/art.42126; online ahead of print). Dr. Mammen's research continues to investigate why some people can safely use statins while others have an increased risk of developing myositis and should avoid this cholesterol-lowering medication.

Staff

Image
Photograph showing faces of the six lab members standing in a line.

Former Lab Members

Postdoctoral Fellows

  • Jose Milisenda, M.D., Ph.D., 2021-2022
  • Jiram Torres Ruiz, M.D., 2021-2022
  • Angela Quintana Vega, Ph.D., 2020-2021
  • Hilal Cevik, M.D., 2019 (2 months)
  • Albert Gil Vila, M.D., 2019 (3 months)
  • Benjamin Plotz, M.D., 2018 (1 month)
  • Sara Sabbagh, D.O., 2017-2019

Pre-doctoral Fellows

  • Bianca Campbell, 2022 (two months)
  • Rose Graf, 2018-2019
  • Rebecca De Lorenzo, 2017
  • Richard Yeker, 2016-2018
  • David Amici, 2016-2017
  • Cassie Parks, 2015-2017
  • Wilson Huang , 2014-2016

Clinical Fellows

  • Matthew Sherman, 2021-2023

Clinical Trials

Recruiting
ClinicalTrials.gov Identifier: NCT05738824

This is an observational study to characterize the different types of inflammatory myopathies, understand their etiology, pathogenesis, prognosis, and response to different treatments. 

Recruiting
ClinicalTrials.gov Identifier: NCT00001265

This study of inflammatory muscle diseases-polymyositis and dermatomyositis and related disorders-will examine what causes these diseases and describe the clinical features (signs and symptoms) associated with them. Inflammation and degeneration of skeletal muscles in these disorders leads to weakness and muscle wasting. The skin, lungs and other organs may also be involved.

Scientific Publications

Selected Recent Publications

Myositis-associated autoantibodies in juvenile myositis are associated with refractory disease and mortality.

Sherman MA, Noroozi Farhadi P, Pak K, Trieu EP, Sarkar K, Targoff IN, Neely ML, Mammen AL, Rider LG, Childhood Myositis Heterogeneity Collaborative Study Group
Arthritis Rheumatol.
2024 Jan 25;
doi: 10.1002/art.42813
PMID: 38272842

Transcriptional derepression of CHD4/NuRD-regulated genes in the muscle of patients with dermatomyositis and anti-Mi2 autoantibodies.

Pinal-Fernandez I, Milisenda JC, Pak K, Muñoz-Braceras S, Casal-Dominguez M, Torres-Ruiz J, Dell'Orso S, Naz F, Gutierrez-Cruz G, Duque-Jaimez Y, Matas-Garcia A, Padrosa J, Garcia-Garcia FJ, Guitart-Mampel M, Garrabou G, Trallero-Araguás E, Walitt B, Paik JJ, Albayda J, Christopher-Stine L, Lloyd TE, Grau-Junyent JM, Selva-O'Callaghan A, Mammen AL
Ann Rheum Dis.
2023 Aug;
82(8).
doi: 10.1136/ard-2023-223873
PMID: 37130727

Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial.

Mammen AL, Amato AA, Dimachkie MM, Chinoy H, Hussain Y, Lilleker JB, Pinal-Fernandez I, Allenbach Y, Boroojerdi B, Vanderkelen M, Delicha EM, Koendgen H, Farzaneh-Far R, Duda PW, Sayegh C, Benveniste O
Lancet Rheumatol.
2023 Feb;
5(2).
doi: 10.1016/s2665-9913(23)00003-6
PMID: 36923454

Autoantibodies Recognizing Specificity Protein 4 Co-occur With Anti-Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis.

Sherman MA, Pak K, Pinal-Fernandez I, Flegel WA, Targoff IN, Miller FW, Rider LG, Mammen AL, Childhood Myositis Heterogeneity Collaborative Study Group
Arthritis Rheumatol.
2023 Sep;
75(9).
doi: 10.1002/art.42512
PMID: 36996276

Transcriptomic profiling reveals distinct subsets of immune checkpoint inhibitor induced myositis.

Pinal-Fernandez I, Quintana A, Milisenda JC, Casal-Dominguez M, Muñoz-Braceras S, Derfoul A, Torres-Ruiz J, Pak K, Dell'Orso S, Naz F, Gutierrez-Cruz G, Milone M, Shelly S, Duque-Jaimez Y, Tobias-Baraja E, Matas-Garcia A, Garrabou G, Padrosa J, Ros J, Trallero-Araguás E, Walitt B, Christopher-Stine L, Lloyd TE, Zhao C, Swift S, Rajan A, Grau-Junyent JM, Selva-O'Callaghan A, Liewluck T, Mammen AL
Ann Rheum Dis.
2023 Jun;
82(6).
doi: 10.1136/ard-2022-223792
PMID: 36801811

Coordinated local RNA overexpression of complement induced by interferon gamma in myositis.

Casal-Dominguez M, Pinal-Fernandez I, Pak K, Muñoz-Braceras S, Milisenda JC, Torres-Ruiz J, Dell Orso S, Naz F, Gutierrez-Cruz G, Duque-Jaimez Y, Matas-Garcia A, Valls-Roca L, Garrabou G, Trallero-Araguas E, Walitt B, Christopher-Stine L, Lloyd TE, Paik JJ, Albayda J, Corse A, Grau JM, Selva-O'Callaghan A, Mammen AL
Sci Rep.
2023 Feb 4;
13(1).
doi: 10.1038/s41598-023-28838-z
PMID: 36739295

The pattern of MHC class I expression in muscle biopsies from patients with myositis and other neuromuscular disorders.

Milisenda JC, Pinal-Fernandez I, Lloyd TE, Grau-Junyent JM, Christopher-Stine L, Corse AM, Mammen AL
Rheumatology (Oxford).
2023 Sep 1;
62(9).
doi: 10.1093/rheumatology/kead052
PMID: 36707996

Clinical Subgroups and Factors Associated With Progression in Patients With Inclusion Body Myositis.

Michelle EH, Pinal-Fernandez I, Casal-Dominguez M, Albayda J, Paik JJ, Tiniakou E, Adler B, Mecoli CA, Danoff SK, Christopher-Stine L, Mammen AL, Lloyd TE
Neurology.
2023 Mar 28;
100(13).
doi: 10.1212/WNL.0000000000206777
PMID: 36690456

Coexisting autoantibodies against transcription factor Sp4 are associated with decreased cancer risk in patients with dermatomyositis with anti-TIF1γ autoantibodies.

Hosono Y, Sie B, Pinal-Fernandez I, Pak K, Mecoli CA, Casal-Dominguez M, Warner BM, Kaplan MJ, Albayda J, Danoff S, Lloyd TE, Paik JJ, Tiniakou E, Aggarwal R, Oddis CV, Moghadam-Kia S, Carmona-Rivera C, Milisenda JC, Grau-Junyent JM, Selva-O'Callaghan A, Christopher-Stine L, Larman HB, Mammen AL
Ann Rheum Dis.
2023 Feb;
82(2).
doi: 10.1136/ard-2022-222441
PMID: 36008132

Anti-FHL1 autoantibodies in juvenile myositis are associated with anti-Ro52 autoantibodies but not with severe disease features.

Sherman MA, Graf R, Sabbagh SE, Galindo-Feria AS, Pinal-Fernandez I, Pak K, Kishi T, Flegel WA, Targoff IN, Miller FW, Lundberg IE, Rider LG, Mammen AL, Childhood Myositis Heterogeneity Collaborative Study Group
Rheumatology (Oxford).
2023 Feb 23;
62(SI2).
doi: 10.1093/rheumatology/keac428
PMID: 35961028

Increased risk of statin-associated autoimmune myopathy among American Indians.

Wei J, Ketner E, Mammen AL
Arthritis Rheumatol.
2022 Sep;
74(9).
doi: 10.1002/art.42126
PMID: 35333459

Key Publications

Machine learning algorithms reveal unique gene expression profiles in muscle biopsies from patients with different types of myositis.

Pinal-Fernandez I, Casal-Dominguez M, Derfoul A, Pak K, Miller FW, Milisenda JC, Grau-Junyent JM, Selva-O'Callaghan A, Carrion-Ribas C, Paik JJ, Albayda J, Christopher-Stine L, Lloyd TE, Corse AM, Mammen AL
Ann Rheum Dis.
2020 Sep;
79(9).
doi: 10.1136/annrheumdis-2019-216599
PMID: 32546599

Identification of distinctive interferon gene signatures in different types of myositis.

Pinal-Fernandez I, Casal-Dominguez M, Derfoul A, Pak K, Plotz P, Miller FW, Milisenda JC, Grau-Junyent JM, Selva-O'Callaghan A, Paik J, Albayda J, Christopher-Stine L, Lloyd TE, Corse AM, Mammen AL
Neurology.
2019 Sep 17;
93(12).
doi: 10.1212/WNL.0000000000008128
PMID: 31434690

Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1.

Mammen AL, Rajan A, Pak K, Lehky T, Casciola-Rosen L, Donahue RN, Lepone LM, Zekeridou A, Pittock SJ, Hassan R, Schlom J, Gulley JL
Ann Rheum Dis.
2019 Jan;
78(1).
doi: 10.1136/annrheumdis-2018-213777
PMID: 30185415

Statin-Associated Autoimmune Myopathy.

Mammen AL
N Engl J Med.
2016 Feb 18;
374(7).
doi: 10.1056/NEJMra1515161
PMID: 26886523

Intravenous Immune Globulin for Statin-Triggered Autoimmune Myopathy.

Mammen AL, Tiniakou E
N Engl J Med.
2015 Oct 22;
373(17).
doi: 10.1056/NEJMc1506163
PMID: 26488714

Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.

Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA
Arthritis Rheum.
2011 Mar;
63(3).
doi: 10.1002/art.30156
PMID: 21360500

News & Highlights

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Understanding Autoimmune Diseases

Sometimes, your immune system makes mistakes. If it sees your body’s healthy cells as a threat, it may attack them. This can cause an autoimmune disorder.