ABOUT AUTOANTIBODIES

Understanding the role of autoantibodies in autoimmune myositis

Autoantibodies are increasingly recognized as important biomarkers in the classification and diagnosis of autoimmune myositis (AIM), with emerging evidence
suggesting potential roles in disease pathophysiology.1

 

Advances in serological profiling continue to refine understanding of disease
heterogeneity and progression in AIM and may help inform clinical management.2

Myositis-specific and myositis-associated autoantibodies2

A growing range of autoantibodies have been identified across AIM subtypes. Myositis-specific autoantibodies (MSAs) are closely associated with distinct phenotypes and are used as biomarkers to facilitate diagnosis and prognosis, while myositis-associated autoantibodies (MAAs) may occur alongside other connective tissue diseases and overlap syndromes.2

Reports suggest autoantibodies are detectable in up to 80% of patients with AIM,3 with some hypothesizing that it is likely the remainder have autoantibodies yet to be discovered.2

Recognition of these antibody profiles has contributed to improved disease classification and a more nuanced understanding of subtype heterogeneity.2

Timeline chart of autoantibodies identified across autoimmune myositis subtypes from 1971 to 2023, with color-coded labels indicating associated clinical phenotypes such as connective tissue disease overlap, lung disease, skin disease, malignancy, inclusion body myositis (IBM), and muscle disease. The chart includes antibodies such as Mi2, Jo1, SRP, MDA5, HMGCR, TIF1γ, NXP2, SAE, cN1a, eIF3, Sp4, and others. The antibodies are grouped with labels indicating whether they are detectable using non-specialist assays or not yet routinely testable.

*Increases risk of ILD, regardless of which other MSA are present
a) concerns about reliability of some assays in current use
b) necrotizing myopathy
c) predominantly found alongside anti-TIF1γ, where their presence reduces cancer risk to a level that is comparable with the general population
d) antisynthetase antibodies
Figure from Harvey G, et al. Curr Rheumatol Rep. 2024;27(1):5. Copyright © Harvey G, et al. Licensed under Creative Commons 4.0 www.creativecommons.org/licenses/by/4.0

Take a deeper look at MSAs and MAAs

Autoantibodies in the pathogenesis of AIM

Mounting evidence suggests that autoantibodies contribute directly to disease pathogenesis in AIM through immune-mediated mechanisms that promote muscle injury and extramuscular organ involvement.1,3,4

Find out how autoantibodies drive disease in AIM

Autoantibodies in the diagnosis of AIM6

Autoantibody testing has become an important component of AIM diagnosis and subtype classification. Serological assessment, alongside clinical evaluation, imaging, and histopathology, can support earlier recognition of disease and identification of clinically relevant phenotypes.4–7

As our understanding of AIM evolves, autoantibody profiling continues to shape diagnostic approaches and clinical decision-making.2,4

Explore the role of autoantibodies in diagnosis
Illustration of a charging bull decorated with antibody symbols, and a yellow glow around his horns, crashing through a room filled with blue and white ceramic pottery, with broken shelves and shattered vases scattered across the floor.

Continue exploring AIM

Learn more about the subtypes of AIM, burden of disease, and current and emerging treatments.

What is AIM?

AIM is a rare autoimmune rheumatic disease spectrum, encompassing heterogeneous subtypes with diverse clinical presentations.8

Learn more about AIM
Burden of disease

AIM can reshape the lives of patients and those around them.9

The burden of AIM
Current treatments

There remains an unmet need for effective and well-tolerated treatments for AIM.10

Current treatments

Abbreviations:
AIM, autoimmune myositis; CCAR-1, cell cycle and apoptosis regulator 1; CN1a, cytosolic 5’-nucleotodase 1A; CTD, connective tissue disease; EJ, glycyl-tRNA synthetase; elF2b, eukaryotic initiation factor 2B; elF3, eukaryotic initiation factor 3; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; ILD, interstitial lung disease; Jo1, histidyl tRNA synthetase; KS, asparaginyl-tRNA synthetase; Ly, cysteinyl-tRNA synthetase; MAA, myositis-associated autoantibody; MDA5, melanoma differentiation-associated gene 5; MSA, myositis-associated autoantibody; NXP2, nuclear matrix protein 2; OJ, isoleucyl-tRNA synthetase; PL7, threonyl-tRNA-synthetase; PL12, alanyl-tRNA synthetase; PMScl, polymyositis–scleroderma overlap; SAE, small ubiquitin-like modified activating enzyme; SMN, survival of motor neuron; Sp4, transcription factor Sp4; SRP, signal recognition particle; TIF1γ, transcription intermediary factor 1-gamma; U1/4/5/6/11/12 RNP, U1/4/5/6/11/12 small nuclear ribonucleoprotein; ZO, phenylalanyl-tRNA synthetase

References:
1. Groener M and Paik J. Front Immunol. 2025;16:1581323; 2. Harvey GR, et al. Curr Rheumatol Rep. 2024;27(1):5; 3. Wu Y, et al. Front Immunol. 2024;15:1439807; 4. Wang G and McHugh NJ. Clin Exp Rheumatol. 2025;43(2):364–71; 5. Diomedi M, et al. Clin Exp Rheumatol. 2026;44(2):167–177; 6. Paik JJ, et al. Rheumatology (Oxford). 2025;64(6):3288–302; 7. Halilu F, Christopher-Stine L. Rheumatol Immunol Res. 2022;3(1):1-10;  8. Lundberg IE, et al. Nat Rev Dis Primers. 2021;7(1):86; 9. Oldroyd A, et al. BMC Rheumatol. 2020;4:47;  10. Natour A, Kivity S. Rambam Maimonides Med J. 2023;14(2):e0008.