Dermatomyositis autoantibodies: how can we maximize utility?

Abstract

The past 15 years has seen significant advances in the characterization of myositis-specific autoantibodies (MSAs) and their associated phenotypes in patients with dermatomyositis (DM). As more careful studies are performed, it is clear that unique combinations of clinical and pathological phenotypes are associated with each MSA, despite the fact that there is considerable heterogeneity within antibody classes as well as overlap across the groups. Because risk for interstitial lung disease (ILD), internal malignancy, adverse disease trajectory, and, potentially response to therapy differ by DM MSA group, a deeper understanding of MSAs and validation and standardization of assays used for detection are critical for optimizing diagnosis and treatment. Like any test, the diagnostic sensitivity and specificity of assays for various MSAs is not perfect. Currently tests for MSAs are helpful at minimum for a clinician to assess relative risk or contribute to diagnosis and perhaps counsel the appropriate patient about what to expect.With international standardization and larger studies it is likely that more antibody tests will make their way into formal schemata for diagnosis and actionable risk assessment in DM. In this review, we summarize key considerations for interpreting the clinical and pathologic associations with MSA in DM and identify critical gaps in knowledge and practice that will maximize their clinical utility and utility for understanding disease pathogenesis.

Clinical Characteristics of Anti-TIF-1γ Antibody-Positive Dermatomyositis Associated with Malignancy

“…Although dermatomyositis (DM) has been recognized as an autoimmune disease, several novel specific autoantibodies have been discovered recently. These include anti-aminoacyl tRNA synthetase (ARS) antibodies, such as the anti-Jo-1 and anti-Mi-2 antibodies, anti-melanoma differentiation-associated gene 5 (MDA-5) antibody, anti-transcriptional intermediary factor 1 (TIF-1γ) antibody, anti-nuclear matrix protein 2 antibodies, and anti-small ubiquitin-like modifier-1 activating enzyme antibody [ 1 , 2 ]. Recently, inflammatory myopathy is classified based on these myositis-specific autoantibodies because each group has unique characteristics [ 3 ], and anti-synthetase syndrome is a new concept to be a differentiated nosological disease from DM.…”

Positioning of myositis-specific and associated autoantibody (MSA/MAA) testing in disease criteria and routine diagnostic work-up

“…It should be noted, however, that also IP may have shortcomings and these assays are not harmonized. Indeed, some workers used K562 cells while others used HeLa cells and it is not unlikely that autoantigen configurations in the extracts vary between cell lines as well as culture conditions [ 47 ]. Some IP studies even use cells that have been transfected with the target antigen in order to increase sensitivity [ 48 ].…”

The Role of Myositis-Specific Autoantibodies in the Dermatomyositis Spectrum

“…DM is marked by a variety of muscle and cutaneous symptoms as well as consequences such as ILD and malignancy [14][15][16][17]. The variability of DM makes diagnosis difficult [18]. Other challenges in diagnosis are assessing the patient for occult malignancy, other orang involvement, and similar clinical presentations to autoimmune rheumatologic disorders like systemic lupus erythematosus, mixed connective tissue disorder, rheumatoid arthritis, cutaneous lupus erythematosus, inflammatory myopathies, and cutaneous eruptions [18].…”

“…The variability of DM makes diagnosis difficult [ 18 ]. Other challenges in diagnosis are assessing the patient for occult malignancy, other orang involvement, and similar clinical presentations to autoimmune rheumatologic disorders like systemic lupus erythematosus, mixed connective tissue disorder, rheumatoid arthritis, cutaneous lupus erythematosus, inflammatory myopathies, and cutaneous eruptions [ 18 ]. DM has a bimodal onset distribution of incidence: onset in childhood between 5 and 10 years of age and in adulthood between 40 and 60 years of age, with a female preponderance [ 17 ].…”

“…(1) Myositis-associated autoantibodies (MAA): anti-PM Scl, anti-U1, anti-U2, anti U3-RNP, anti-Hu anti-SSA/anti-Ro and anti-Sjogren's syndrome B (anti-SSB)/anti-La autoantibodies [ 17 ]. (2) Myositis-specific autoantibodies (MSA): anti-Mi-2, anti-melanoma differentiation-associated protein-5 (anti-MDA-5), anti-nuclear matrix protein-2 (anti-NXP-2),anti -TIF-1 and anti-small ubiquitin-like modifier activating enzyme (anti-SAE)-1/2 [ 7 , 14 , 15 , 17 , 18 ].…”