A wide spectrum of clinical manifestations is seen in idiopathic inflammatory myositis, but the underlying pathogenesis is still murky. Dr. Fiorentino says one of the next steps in myositis research is understanding the biology of these antigens.
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Explore This IssueJanuary 2020
“We need to understand where these antigens are and in which types of cells. Antigen structure is going to play a large role in understanding how the immune response is being generated in the tissue,” he says. “We don’t understand why these antibodies are generated against proteins which are ubiquitously expressed in all of our tissues.”
Dr. Christopher-Stine anticipates a role for precision medicine in the future of the field: “Precision medicine is most exciting on two fronts: fine-tuning which patients will develop which complications and designing better treatment algorithms.” She explains how further genomic studies may allow for a more personalized selection of immunosuppressant therapy. Additionally, she believes we can improve the criteria for inflammatory myopathies. The 2017 ACR/EULAR Criteria for Idiopathic Inflammatory Myopathies include only one myositis-specific antibody, anti-Jo1.
“I think we can go a step further, since autoantibodies drive the phenotypes so strongly, yet they were not included,” says Dr. Christopher-Stine.
An appreciation for the cutaneous and other clinical manifestations associated with myositis-specific antibodies has implications for diagnosis and management, particularly with rarer subtypes of idiopathic inflammatory myopathies. When evaluating a patient with suspected inflammatory myopathy, cutaneous ulcerations or palmar papules should raise concern for possible MDA5-associated dermatomyositis, and an ovoid palatal lesion should raise suspicion for possible TIF1-γ-associated myositis. The presence of certain myositis-specific antibodies requires additional management considerations, including cancer screening in TIF1-γ patients given the strong association with malignancy in those patients. By further identifying and studying these novel phenotypes associated with myositis antibodies in IIM, we can substratify patients and better understand the underlying disease pathogenesis and potential therapeutic targets.
Mithu Maheswaranathan, MD, is a rheumatology fellow at Duke University Medical Center, Durham, N.C.
Lisa Criscione-Schreiber, MD, MEd, is associate professor of medicine at Duke University School of Medicine, Durham, N.C.
All the ACR-endorsed criteria.
- Merlo G, Clapasson A, Cozzani E, et al. Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets. Arch Dermatol Res. 2017 Mar;309(2):87–95. Epub 2016 Dec 7.
- Oldroyd A, Lilleker J, Chinoy H. Idiopathic inflammatory myopathies—a guide to subtypes, diagnostic approach and treatment. Clin Med (Lond). 2017 Jul;17(4):322–328.
- Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344–347.
- Lundberg IE, Tjärnlund A, Bottai M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017 Dec;76(12):1955–1964.
- Fujimoto M, Watanabe R, Ishitsuka Y, et al. Recent advances in dermatomyositis-specific autoantibodies. Curr Opin Rheumatol. 2016 Nov;28(6):636–644.
- Fiorentino D, Chung L, Zwerner J, et al. The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): A retrospective study. J Am Acad Dermatol. 2011 Jul;65(1):25–34.
- Gono T, Sato S, Kawaguchi Y, et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford). 2012 Sep;51(9):1563–1570.
- Bernet LL, Lewis MA, Rieger KE, et al. Ovoid palatal patch in dermatomyositis: A novel finding associated with anti-TIF1γ (p155) antibodies. JAMA Dermatol. 2016 Sep 1;152(9):1049–1051.
- Wolstencroft PW, Fiorentino DF. Dermatomyositis clinical and pathological phenotypes associated with myositis-specific autoantibodies. Curr Rheumatol Rep. 2018 Apr;20(5):28.
- Yang Y, Yin G, Hao J, et al. Serum interleukin-18 level is associated with disease activity and interstitial lung disease in patients with dermatomyositis. Arch Rheumatol. 2017 Apr 11;32(3):181–188.
- Moghadam-Kia S, Oddis CV, Aggarwal R. Anti-MDA5 antibody spectrum in Western World. Curr Rheumatol Rep. 2018 Oct 31;
- Albayda J, Khan A, Casciola-Rosen L, et al. Inflammatory myopathy associated with anti-mitochondrial antibodies: A distinct phenotype with cardiac involvement. Semin Arthritis Rheum. 2018 Feb;47(4):552–556.