Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Rheumatology Reports
Published in: Current Rheumatology Reports 3/2010

01-06-2010

Dermatomyositis and Type 1 Interferons

Author: Steven A. Greenberg

Published in: Current Rheumatology Reports | Issue 3/2010

Login to get access

Abstract

Dermatomyositis is a poorly understood multisystem disease predominantly affecting skin and muscle. This review focuses on the potential role of a group of related cytokines, the type 1 interferons, in the pathogenesis of dermatomyositis. Type 1 interferon–inducible transcripts and proteins are uniquely elevated in dermatomyositis muscle compared with all other muscle diseases studied to date. The endothelial cell tubuloreticular inclusions present in affected dermatomyositis muscle are biomarkers of type 1 interferon exposure. The cell-poor lichenoid reaction in skin with predominant involvement of the basal epidermal cell layer and its topologic equivalent in muscle, perifascicular atrophy, may be lesions that develop directly in response to type 1 interferon signaling.
Literature
1.
2.
Greenberg SA: Type 1 interferons and myositis. Arthritis Res Ther 2010, 12(Suppl 1):S4.
3.
•• Salajegheh M, Kong SK, Pinkus JL, et al.: Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy. Ann Neurol 2010, 67:53–63. This study demonstrates the remarkable specificity of a high abundance of ISG15 transcript for dermatomyositis muscle, that ISG15 protein is conjugated to multiple other proteins in dermatomyositis muscle, and that the exposure of muscle cell culture to type 1 interferons produces a molecular picture highly similar to that of human dermatomyositis muscle.
4.
5.
6.
Norton WL, Velayos E, Robison L: Endothelial inclusions in dermatomyositis. Ann Rheum Dis 1970, 29:67–72.CrossRefPubMed
7.
Banker BQ: Dermatomyostis of childhood, ultrastructural alteratious of muscle and intramuscular blood vessels. J Neuropathol Exp Neurol 1975, 34:46–75.CrossRefPubMed
8.
Carpenter S, Karpati G, Rothman S, Watters G: The childhood type of dermatomyositis. Neurology 1976, 26:952–962.PubMed
9.
De Visser M, Emslie-Smith AM, Engel AG: Early ultrastructural alterations in adult dermatomyositis. Capillary abnormalities precede other structural changes in muscle. J Neurol Sci 1989, 94:181–192.CrossRefPubMed
10.
Kissel JT, Halterman RK, Rammohan KW, Mendell JR: The relationship of complement-mediated microvasculopathy to the histologic features and clinical duration of disease in dermatomyositis. Arch Neurol 1991, 48:26–30.PubMed
11.
Kissel JT, Mendell JR, Rammohan KW: Microvascular deposition of complement membrane attack complex in dermatomyositis. N Engl J Med 1986, 314:329–334.PubMedCrossRef
12.
Emslie-Smith AM, Engel AG: Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol 1990, 27:343–356.CrossRefPubMed
13.
• Greenberg SA: Proposed immunologic models of the inflammatory myopathies and potential therapeutic implications. Neurology 2007, 69:2008–2019. This review of dermatomyositis, polymyositis, and inclusion body myositis disease mechanism outlines a model of myofiber injury stemming directly from the intracellular production of type 1 interferons.
14.
Greenberg SA, Amato AA: Uncertainties in the pathogenesis of adult dermatomyositis. Curr Opin Neurol 2004, 17:359–364.CrossRefPubMed
15.
•• Sontheimer RD: Lichenoid tissue reaction/interface dermatitis: clinical and histological perspectives. J Invest Dermatol 2009, 129:1088–1099. This is a review of a class of disorders characterized by lichenoid tissue reactions.
16.
• Crowson AN, Magro CM, Mihm MC Jr: Interface dermatitis. Arch Pathol Lab Med 2008, 132:652–666. The use of the term interface dermatitis is described, and skin diseases with this pathology are reviewed.
17.
Crowson AN, Magro CM: The role of microvascular injury in the pathogenesis of cutaneous lesions of dermatomyositis. Hum Pathol 1996, 27:15–19.CrossRefPubMed
18.
• Wenzel J, Tuting T: An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in “interface dermatitis.” J Invest Dermatol 2008, 128:2392–2402. This review advocates for a general role of type 1 interferons in many skin disorders characterized by an interface dermatitis. It advocates for a mechanism by which type 1 interferons exert their injurious effects through activation of cytotoxic T cells.
19.
• Greenberg SA, Fiorentino D: Similar topology of injury to keratinocytes and myofibres in dermatomyositis skin and muscle. Br J Dermatol 2009, 160:464–465. This brief letter notes that perifascicular atrophy in dermatomyositis muscle has the same topology as the lichenoid tissue reaction in skin.
20.
Grimley PM, Davis GL, Kang YH, et al.: Tubuloreticular inclusions in peripheral blood mononuclear cells related to systemic therapy with alpha-interferon. Lab Invest 1985, 52:638–649.PubMed
21.
Kuyama J, Kanayama Y, Mizutani H, et al.: Formation of tubuloreticular inclusions in mitogen-stimulated human lymphocyte cultures by endogenous or exogenous alpha-interferon. Ultrastruct Pathol 1986, 10:77–85.CrossRefPubMed
22.
Feldman D, Goldstein AL, Cox DC, Grimley PM: Cultured human endothelial cells treated with recombinant leukocyte A interferon. Tubuloreticular inclusion formation, antiproliferative effect, and 2′,5′ oligoadenylate synthetase induction. Lab Invest 1988, 58:584–589.PubMed
23.
Rich SA, Owens TR, Bartholomew LE, Gutterman JU: Immune interferon does not stimulate formation of alpha and beta interferon induced human lupus-type inclusions. Lancet 1983, 1:127–128.CrossRefPubMed
24.
Greenberg SA, Pinkus JL, Pinkus GS, et al.: Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis. Ann Neurol 2005, 57:664–678.CrossRefPubMed
25.
•• Walsh RJ, Kong SW, Yao Y, et al.: Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum 2007, 56:3784–3792. This study demonstrates the marked abundance of type 1 interferon–inducible transcripts in blood samples from patients with active dermatomyositis, and to a lesser extent polymyositis.
26.
• Greenberg SA: A gene expression approach to study perturbed pathways in myositis. Curr Opin Rheumatol 2007, 19:536–541. This review outlines how gene expression studies have led to new discoveries in myositis research.
27.
Kea B, Pesich R, Chung LS, et al.: Genomic analyses identify lipid metabolism abnormalities in dermatomyositis patients [abstract]. J Invest Dermatol 2007, 127(Suppl 1):S12.
28.
• Magro CM, Segal JP, Neil Crowson A, Chadwick P: The phenotypic profile of dermatomyositis and lupus erythematosus: a comparative analysis. J Cutan Pathol 2009 Nov 4 (Epub ahead of print). This study demonstrates MxA expression in endothelial cells and keratinocytes in dermatomyositis skin.
29.
López de Padilla CM, Vallejo AN, McNallan KT, et al.: Plasmacytoid dendritic cells in inflamed muscle of patients with juvenile dermatomyositis. Arthritis Rheum 2007, 56:1658–1668.CrossRef
30.
Wenzel J, Schmidt R, Proelss J, et al.: Type I interferon-associated skin recruitment of CXCR3+ lymphocytes in dermatomyositis. Clin Exp Dermatol 2006, 31:576–582.CrossRefPubMed
31.
McNiff JM, Kaplan DH: Plasmacytoid dendritic cells are present in cutaneous dermatomyositis lesions in a pattern distinct from lupus erythematosus. J Cutan Pathol 2008, 35:452–456.CrossRefPubMed
32.
•• Liao A, Salajegheh M, Morehouse C, et al.: Human plasmacytoid dendritic cell accumulation amplifies their type 1 interferon production. Clin Immunol 2010 Epub ahead of print. Human pDCs become far more efficient producers of type 1 interferons when they accumulate in concentrations exceeding those normally present in blood. This provides a potential mechanism for marked amplification of type 1 interferon–mediated responses in autoimmune disease tissue sites. Blockade of the type 1 interferon receptor is predicted to diminish type 1 interferon production.
33.
Chen SC, de Groot M, Kinsley D, et al.: Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions. Arch Dermatol Res 2010, 302:113–123.CrossRefPubMed
34.
Varughese N, Petrella T, Singer M, Carlson JA: Plasmacytoid (CD68 + CD123+) monocytes may play a crucial role in the pathogenesis of hydroa vacciniforme: a case report. Am J Dermatopathol 2009, 31:828–833.CrossRefPubMed
35.
•• Sato S, Hoshino K, Satoh T, et al.: RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum 2009, 60:2193–2200. Autoantibodies against a type 1 interferon–inducible protein are highly sensitive and specific to clinical amyopathic dermatomyositis across a broad range of rheumatologic diseases. This provides evidence that these autoantibodies are downstream events following type 1 interferon signaling.
36.
Mammen AL, Casciola-Rosen LA, Hall JC, et al.: Expression of the dermatomyositis autoantigen Mi-2 in regenerating muscle. Arthritis Rheum 2009, 60:3784–3793.CrossRefPubMed
37.
Casciola-Rosen L, Nagaraju K, Plotz P, et al.: Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy. J Exp Med 2005, 201:591–601.CrossRefPubMed
38.
• Indraccolo S, Pfeffer U, Minuzzo S, et al.: Identification of genes selectively regulated by IFNs in endothelial cells. J Immunol 2007, 178:1122–1135. This study explored the transcriptional effects of interferons on endothelial cells toward a goal of understanding further their antiangiogenic effects.
39.
• Indraccolo S: Interferon-alpha as angiogenesis inhibitor: learning from tumor models. Autoimmunity 2010 Feb 19 (Epub ahead of print). The angiogenic and angiostatic effects of interferon-α are reviewed.
40.
Folkman J: Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 2007, 6:273–286.CrossRefPubMed
Metadata
Title
Dermatomyositis and Type 1 Interferons
Author
Steven A. Greenberg
Publication date
01-06-2010
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 3/2010
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-010-0101-6

Other articles of this Issue 3/2010

Current Rheumatology Reports 3/2010 Go to the issue

ReviewPaper

Cutaneous Manifestations of Dermatomyositis and Their Management

ReviewPaper

Drug-related Myopathies of Which the Clinician Should Be Aware

ReviewPaper

Mechanical Factors and Bone Health: Effects of Weightlessness and Neurologic Injury

ReviewPaper

Update on the Assessment of Children with Juvenile Idiopathic Inflammatory Myopathy

ReviewPaper

Bone Changes and Fracture Risk in Individuals Infected With HIV

ReviewPaper

The Societal Burden of Osteoporosis
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits