Idiopathic Inflammatory Myopathies: Laboratory Support for Diagnosis
Idiopathic Inflammatory Myopathies: Laboratory Support for Diagnosis
This Clinical Focus provides an overview of the use of laboratory testing to diagnose myositis caused by the idiopathic inflammatory myopathies.
Clinical Focus
Idiopathic Inflammatory Myopathies
Laboratory Support for Diagnosis
Clinical background [return to contents]
The idiopathic inflammatory myopathies (IIMs) are a group of systemic autoimmune diseases characterized by muscle inflammation (myositis) and weakness. IIMs are rare, affecting 3 to 34 in 100,000 people,1 and can affect both adults and children. In addition to muscle weakness, manifestations can include skin rashes, arthritis, dysphagia, and Raynaud phenomenon. Common complications include interstitial lung disease, cancer, and cardiac involvement, which are the leading causes of death in IIMs.1,2
Antibodies considered to be myositis-specific autoantibodies (MSAs) define the major IIM subtypes, which differ in distribution, clinical presentation, and autoantibody profile (Table 1), though considerable heterogeneity exists.8 IIMs can also occur with other autoimmune rheumatic diseases, such as Sjögren syndrome, systemic sclerosis, and systemic lupus erythematosus, which is known as overlap myositis. Antibodies called myositis-associated autoantibodies (MAAs) may help identify these conditions.
Table 1. Features of IIM Subtypes [return to contents]
Subtypea |
Peak age(s) of onset, years3,4 |
Sex distribution1,3 |
Symptoms1,3–5 |
Complications3,4 |
Associated autoantibodies1,6,7 |
ASyS |
50 |
Female predominance |
|
|
|
DM |
5-15 (juvenile DM), |
Female predominance |
|
|
|
IBM |
>50 |
Male predominance |
|
|
|
IMNM |
30-70 |
Female predominance |
|
|
|
Overlap myositis |
<50 |
Female predominance |
|
|
|
| ASyS, antisynthetase syndrome; cN-1A, cytosolic 5′-nucleotidase 1A; DM, dermatomyositis; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; IBM, inclusion body myositis; IIM, idiopathic inflammatory myopathy; ILD, interstitial lung disease; IMNM, immune-mediated necrotizing myopathy; MDA-5, melanoma differentiation-associated protein 5; MSA, myositis-specific autoantibody; NXP-2, nuclear matrix protein 2; RNP, ribonucleoprotein; SRP, signal recognition particle; SS-A, Sjögren syndrome antigen A; TIF1-γ, transcription intermediary factor 1 gamma. | |
| a | Owing to the discovery of MSAs and the identification of other subtypes, polymyositis is now considered a diagnosis of exclusion. Many patients who were previously diagnosed with polymyositis are now classified as having another subtype based on autoantibody profile.1,4 |
Diagnosis of IIM involves (1) excluding conditions with similar presentation (eg, muscular dystrophy and myopathies of known cause) and (2) identifying the IIM subtype.1,9 Evaluation may include electromyography, imaging, biopsy, and laboratory tests for muscle enzymes and autoantibodies.1,5
This Clinical Focus provides information about laboratory tests that are useful in diagnosing IIMs. This information is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.
Individuals suitable for testing [return to contents]
- Individuals with symptoms of IIM (Table 1)
Test availability [return to contents]
Quest Diagnostics offers several tests and panels that may be useful for diagnosing IIMs (Table 2).
Table 2. Laboratory Tests for Diagnosis of IIMs [return to contents]
Test code |
Test name |
Clinical use |
Muscle enzyme tests |
||
823 |
Alanine Aminotransferase (ALT) |
Diagnose IIM |
227 |
Aldolase |
Diagnose IIM |
822 |
Aspartate Aminotransferase (AST) |
Diagnose IIM |
374 |
Creatine Kinase (CK), Total |
Diagnose IIM |
593 |
Lactate Dehydrogenase (LD) |
Diagnose IIM |
Autoantibody panels |
||
10257 |
Extended Myositis Specific Antibody (MSA) Panela,b Includes cytosolic 5′-nucleotidase 1A (cN-1A, IgG, test code 10266), EJ, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR, IgG, test code 39044), Jo-1, MDA-5, Mi-2α, Mi-2β, NXP-2, OJ, PL-7, PL-12, SRP, and TIF1-γ antibodies. |
Diagnose ASyS, DM, IBM, and IMNM |
39149 |
Interstitial Lung Disease Panela,b Includes centromere A and B, cyclic citrullinated peptide (CCP, IgG, test code 11173), EJ, fibrillarin, Jo-1, Ku, MDA-5, mutated citrullinated vimentin (MCV, test code 13828), OJ, PL-7, PL-12, PM/Scl-75, PM/Scl-100, rheumatoid factor (test code 4418), RNA polymerase III (test code 19899), RNP (test code 19887), SS-A, Scl-70, and Th/To antibodies. |
Diagnose overlap of IIM and MCTD, RA, SLE, SS, or SSc Identify connective tissue disease as a possible cause of interstitial lung disease |
94777 |
Myositis Specific 11 Antibody Panela Includes EJ, Jo-1, MDA-5, Mi-2α, Mi-2β, NXP-2, OJ, PL-7, PL-12, SRP, and TIF1-γ antibodies. |
Diagnose ASyS, DM, and IMNM |
Individual autoantibody tests |
||
94646 |
Anti-PM/Scl-100 Abc |
Diagnose overlap of IIM and SSc |
10266 |
Cytosolic 5′-Nucleotidase 1A (cN-1A) Antibody (IgG)b |
Diagnose IBM |
34262 |
Fibrillarin (U3 RNP) Antibody, IgGd |
Diagnose overlap of IIM and SSc |
39044 |
3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMGCR) Antibody (IgG) |
Diagnose IMNM |
5810 |
Jo-1 Antibody |
Diagnose ASyS |
19887 |
RNP Antibody |
Diagnose overlap of IIM and MCTD, SLE, or SSc |
38568 |
Sjögren's Antibody (SS-A) |
Diagnose overlap of IIM and SLE, SS, or SSc |
38567 |
Sm/RNP Antibody |
Diagnose overlap of IIM and MCTD, SLE, or SSc |
| ASyS, antisynthetase syndrome; CLIA, Clinical Laboratory Improvement Amendments; DM, dermatomyositis; IBM, inclusion body myositis; IIM, idiopathic inflammatory myopathy; IMNM, immune-mediated necrotizing myopathy; MCTD, mixed connective tissue disease; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SS, Sjögren syndrome; SSc, systemic sclerosis. | |
| a | This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes. |
| b | Panel components may be ordered separately. |
| c | This test was developed and its performance characteristics have been determined by Labcorp. It has not been cleared or approved by the US Food and Drug Administration. This test is performed in a CLIA-certified laboratory and is intended for clinical purposes. |
| c | This test was developed and its performance characteristics have been determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test is performed in a CLIA-certified laboratory and is intended for clinical purposes. |
Test selection and interpretation [return to contents]
Laboratory workup for suspected IIM includes testing muscle enzyme levels in serum and testing for the presence of MSAs and MAAs.
Muscle enzymes
Patients with IIM often have elevated levels of muscle enzymes in serum, indicating active muscle disease.1,4,5 An elevated level of any of the following enzymes is consistent with IIM: creatine kinase (test code 374), lactate dehydrogenase (test code 593), aspartate aminotransferase (test code 822), alanine aminotransferase (test code 823), and aldolase (test code 227).1,9 Creatine kinase is the most sensitive muscle enzyme1,5; patients with IIM often have creatine kinase levels up to 50 times the upper limit of normal (ULN), with the highest levels seen in immune-mediated necrotizing myopathy (IMNM, up to 100 times the ULN) and the lowest seen in inclusion body myositis (IBM, up to 10 times the ULN).5 However, not all patients with IIM have elevated muscle enzyme levels, especially those with IBM and amyopathic dermatomyositis.1
Autoantibodies
Consensus guidelines from the European Neuromuscular Centre (ENMC) include testing for MSAs and MAAs (Table 3) as part of an optimal testing strategy for suspected IIM.8 MSAs and MAAs are found in up to 80% of patients with IIM5 and are strongly associated with homogenous patient subgroups. MSAs are virtually 100% specific for IIM,6,7 and individual MSAs, which are usually mutually exclusive, are highly specific for certain IIM subtypes. MAAs are often found in IIM but are not specific for it6,7; they can also be found in other autoimmune rheumatic diseases and thus are associated with overlap myositis.1,6
Quest offers testing in accordance with the ENMC’s optimal testing strategy, which includes testing most MSAs.8 Quest’s MSA panels include the Extended Myositis Panel (test code 10257) and the Myositis Specific 11 Antibody Panel (test code 94777), which does not include cN-1A (test code 10266) or HMGCR (test code 39044) antibodies (available individually). Jo-1 antibody is also available individually (test code 5810).
If any autoantibody result is positive, further autoantibody testing may not be necessary, as patients rarely have more than 1 type of MSA (estimated prevalence, 0.11%).7,13 However, if all MSAs are negative, testing for MAAs may be appropriate. Quest offers individual tests for fibrillarin (U3 RNP, test code 34262), PM/Scl-100 (test code 94646), RNP (test code 19887), SS-A (test code 38568), and Sm/RNP (test code 38567). These and additional MAAs (Ku and PM/Scl-75) are available in the Interstitial Lung Disease panel (test code 39149), which includes 20 autoantibodies found in connective tissue diseases associated with interstitial lung disease.
The presence of an MSA or MAA is highly suggestive of IIM. Individual autoantibodies are highly specific for IIM subtypes and may be associated with certain clinical features, complications, and outcomes (Table 3).1,6,7 The absence of MSAs and MAAs does not rule out IIM, as up to 30% of patients with IIM do not have these autoantibodies.1 Some of these patients may have seronegative IMNM, which has no known autoantibody associations.1,4
Table 3. Clinical Significance of Autoantibodies in IIMs [return to contents]
| Autoantibody | Clinical associations1,2,4,6,7,10–12 |
IIM subtypea |
MSAs |
||
Jo-1 |
|
ASyS highly likely |
PL-7 |
|
|
PL-12 |
||
EJ |
|
|
OJ |
|
|
Mi-2α |
|
DM highly likely |
Mi-2β |
||
MDA-5 |
|
|
NXP-2 |
|
|
TIF1-γ |
|
|
cN-1A |
|
IBM likely |
SRP |
|
IMNM highly likely |
HMGCR |
|
|
MAAs |
||
Fibrillarin (U3 RNP) |
|
Overlap myositis likely |
Ku |
|
|
PM/Scl-75 |
|
|
PM/Scl-100 |
||
U1 RNP |
|
|
SS-A |
|
|
| ASyS, antisynthetase syndrome; cN-1A, cytosolic 5′-nucleotidase 1A; DM, dermatomyositis; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; IBM, inclusion body myositis; IIM, idiopathic inflammatory myopathy; ILD, interstitial lung disease; IMNM, immune-mediated necrotizing myopathy; MAA, myositis-associated autoantibody; MCTD, mixed connective tissue disease; MDA-5, melanoma differentiation-associated protein 5; MSA, myositis-specific autoantibody; NXP-2, nuclear matrix protein 2; RNP, ribonucleoprotein; SLE, systemic lupus erythematosus; SRP, signal recognition particle; SS, Sjögren syndrome; SSc, systemic sclerosis; SS-A, Sjögren syndrome antigen A; TIF1-γ, transcription intermediary factor 1 gamma. | |
| a | When clinical features are consistent. |
| b | Because of the rarity of these autoantibodies, clinical associations have not yet been established. |
| c | cN-1A is commonly considered an MSA but is not 100% specific for IIM.6,7 |
References [return to contents]
- Lundberg IE, Fujimoto M, Vencovsky J, et al. Idiopathic inflammatory myopathies. Nat Rev Dis Prim. 2021;7(1):86. doi:10.1038/s41572-021-00321-x
- Oldroyd AGS, Callen JP, Chinoy H, et al. International guideline for idiopathic inflammatory myopathy-associated cancer screening: an International Myositis Assessment and Clinical Studies Group (IMACS) initiative. Nat Rev Rheumatol. 2023;19(12):805-817. doi:10.1038/s41584-023-01045-w
- van Rilland EDZ, Yao L, Stevens KJ, et al. Myositis and its mimics: guideline updates, MRI characteristics, and new horizons. Am J Roentgenol. 2024;223(2):e2431359. doi:10.2214/ajr.24.31359
- Tsamis KI, Boutsoras C, Kaltsonoudis E, et al. Clinical features and diagnostic tools in idiopathic inflammatory myopathies. Crit Rev Clin Lab Sci. 2022;59(4):219-240. doi:10.1080/10408363.2021.2000584
- Dalakas MC. Chapter 18: Autoimmune inflammatory myopathies. In: Younger DS, ed. Motor System Disorders, Part I: Normal Physiology and Function and Neuromuscular Disorders. Vol 195. Handbook of Clinical Neurology. Elsevier; 2023:425-460. doi:10.1016/b978-0-323-98818-6.00023-6
- Ogawa-Momohara M, Muro Y. Myositis-specific and myositis-associated autoantibodies: their clinical characteristics and potential pathogenic roles. Immunol Med. 2024. doi:10.1080/25785826.2024.2413604
- Halilu F, Christopher-Stine L. Myositis-specific antibodies: overview and clinical utilization. Rheumatol Immunol Res. 2022;3(1):1-10. doi:10.2478/rir-2022-0001
- Damoiseaux J, Mammen AL, Piette Y, et al. 256th ENMC International Workshop: myositis specific and associated autoantibodies (MSA-ab), Amsterdam, The Netherlands, 8-10 October 2021. Neuromuscul Disord. 2022;32(7):594-608. doi:10.1016/j.nmd.2022.05.011
- 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;76(12):1955. doi:10.1136/annrheumdis-2017-211468
- Kwiatkowska D, Reich A. The significance of autoantibodies in juvenile dermatomyositis. BioMed Res Int. 2021;2021(1):551354. doi:10.1155/2021/5513544
- Salam S, Dimachkie MM, Hanna MG, et al. Diagnostic and prognostic value of anti-cN1A antibodies in inclusion body myositis. Clin Exp Rheumatol. 2022;40(2):384-393. doi:10.55563/clinexprheumatol/r625rm
- Satoh M, Ceribelli A, Hasegawa T, et al. Clinical Significance of Antinucleolar Antibodies: Biomarkers for Autoimmune Diseases, Malignancies, and others. Clin Rev Allergy Immunol. 2022;63(2):210-239. doi:10.1007/s12016-022-08931-3
- Lega JC, Fabien N, Reynaud Q, et al. The clinical phenotype associated with myositis-specific and associated autoantibodies: A meta-analysis revisiting the so-called antisynthetase syndrome. Autoimmun Rev. 2014;13(9):883-891. doi:10.1016/j.autrev.2014.03.004
Content reviewed 3/2025
This Clinical Focus provides an overview of the use of laboratory testing to diagnose myositis caused by the idiopathic inflammatory myopathies.
Clinical Focus
Idiopathic Inflammatory Myopathies
Laboratory Support for Diagnosis
Clinical background [return to contents]
The idiopathic inflammatory myopathies (IIMs) are a group of systemic autoimmune diseases characterized by muscle inflammation (myositis) and weakness. IIMs are rare, affecting 3 to 34 in 100,000 people,1 and can affect both adults and children. In addition to muscle weakness, manifestations can include skin rashes, arthritis, dysphagia, and Raynaud phenomenon. Common complications include interstitial lung disease, cancer, and cardiac involvement, which are the leading causes of death in IIMs.1,2
Antibodies considered to be myositis-specific autoantibodies (MSAs) define the major IIM subtypes, which differ in distribution, clinical presentation, and autoantibody profile (Table 1), though considerable heterogeneity exists.8 IIMs can also occur with other autoimmune rheumatic diseases, such as Sjögren syndrome, systemic sclerosis, and systemic lupus erythematosus, which is known as overlap myositis. Antibodies called myositis-associated autoantibodies (MAAs) may help identify these conditions.
Table 1. Features of IIM Subtypes [return to contents]
Subtypea |
Peak age(s) of onset, years3,4 |
Sex distribution1,3 |
Symptoms1,3–5 |
Complications3,4 |
Associated autoantibodies1,6,7 |
ASyS |
50 |
Female predominance |
|
|
|
DM |
5-15 (juvenile DM), |
Female predominance |
|
|
|
IBM |
>50 |
Male predominance |
|
|
|
IMNM |
30-70 |
Female predominance |
|
|
|
Overlap myositis |
<50 |
Female predominance |
|
|
|
| ASyS, antisynthetase syndrome; cN-1A, cytosolic 5′-nucleotidase 1A; DM, dermatomyositis; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; IBM, inclusion body myositis; IIM, idiopathic inflammatory myopathy; ILD, interstitial lung disease; IMNM, immune-mediated necrotizing myopathy; MDA-5, melanoma differentiation-associated protein 5; MSA, myositis-specific autoantibody; NXP-2, nuclear matrix protein 2; RNP, ribonucleoprotein; SRP, signal recognition particle; SS-A, Sjögren syndrome antigen A; TIF1-γ, transcription intermediary factor 1 gamma. | |
| a | Owing to the discovery of MSAs and the identification of other subtypes, polymyositis is now considered a diagnosis of exclusion. Many patients who were previously diagnosed with polymyositis are now classified as having another subtype based on autoantibody profile.1,4 |
Diagnosis of IIM involves (1) excluding conditions with similar presentation (eg, muscular dystrophy and myopathies of known cause) and (2) identifying the IIM subtype.1,9 Evaluation may include electromyography, imaging, biopsy, and laboratory tests for muscle enzymes and autoantibodies.1,5
This Clinical Focus provides information about laboratory tests that are useful in diagnosing IIMs. This information is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.
Individuals suitable for testing [return to contents]
- Individuals with symptoms of IIM (Table 1)
Test availability [return to contents]
Quest Diagnostics offers several tests and panels that may be useful for diagnosing IIMs (Table 2).
Table 2. Laboratory Tests for Diagnosis of IIMs [return to contents]
Test code |
Test name |
Clinical use |
Muscle enzyme tests |
||
823 |
Alanine Aminotransferase (ALT) |
Diagnose IIM |
227 |
Aldolase |
Diagnose IIM |
822 |
Aspartate Aminotransferase (AST) |
Diagnose IIM |
374 |
Creatine Kinase (CK), Total |
Diagnose IIM |
593 |
Lactate Dehydrogenase (LD) |
Diagnose IIM |
Autoantibody panels |
||
10257 |
Extended Myositis Specific Antibody (MSA) Panela,b Includes cytosolic 5′-nucleotidase 1A (cN-1A, IgG, test code 10266), EJ, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR, IgG, test code 39044), Jo-1, MDA-5, Mi-2α, Mi-2β, NXP-2, OJ, PL-7, PL-12, SRP, and TIF1-γ antibodies. |
Diagnose ASyS, DM, IBM, and IMNM |
39149 |
Interstitial Lung Disease Panela,b Includes centromere A and B, cyclic citrullinated peptide (CCP, IgG, test code 11173), EJ, fibrillarin, Jo-1, Ku, MDA-5, mutated citrullinated vimentin (MCV, test code 13828), OJ, PL-7, PL-12, PM/Scl-75, PM/Scl-100, rheumatoid factor (test code 4418), RNA polymerase III (test code 19899), RNP (test code 19887), SS-A, Scl-70, and Th/To antibodies. |
Diagnose overlap of IIM and MCTD, RA, SLE, SS, or SSc Identify connective tissue disease as a possible cause of interstitial lung disease |
94777 |
Myositis Specific 11 Antibody Panela Includes EJ, Jo-1, MDA-5, Mi-2α, Mi-2β, NXP-2, OJ, PL-7, PL-12, SRP, and TIF1-γ antibodies. |
Diagnose ASyS, DM, and IMNM |
Individual autoantibody tests |
||
94646 |
Anti-PM/Scl-100 Abc |
Diagnose overlap of IIM and SSc |
10266 |
Cytosolic 5′-Nucleotidase 1A (cN-1A) Antibody (IgG)b |
Diagnose IBM |
34262 |
Fibrillarin (U3 RNP) Antibody, IgGd |
Diagnose overlap of IIM and SSc |
39044 |
3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMGCR) Antibody (IgG) |
Diagnose IMNM |
5810 |
Jo-1 Antibody |
Diagnose ASyS |
19887 |
RNP Antibody |
Diagnose overlap of IIM and MCTD, SLE, or SSc |
38568 |
Sjögren's Antibody (SS-A) |
Diagnose overlap of IIM and SLE, SS, or SSc |
38567 |
Sm/RNP Antibody |
Diagnose overlap of IIM and MCTD, SLE, or SSc |
| ASyS, antisynthetase syndrome; CLIA, Clinical Laboratory Improvement Amendments; DM, dermatomyositis; IBM, inclusion body myositis; IIM, idiopathic inflammatory myopathy; IMNM, immune-mediated necrotizing myopathy; MCTD, mixed connective tissue disease; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SS, Sjögren syndrome; SSc, systemic sclerosis. | |
| a | This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes. |
| b | Panel components may be ordered separately. |
| c | This test was developed and its performance characteristics have been determined by Labcorp. It has not been cleared or approved by the US Food and Drug Administration. This test is performed in a CLIA-certified laboratory and is intended for clinical purposes. |
| c | This test was developed and its performance characteristics have been determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test is performed in a CLIA-certified laboratory and is intended for clinical purposes. |
Test selection and interpretation [return to contents]
Laboratory workup for suspected IIM includes testing muscle enzyme levels in serum and testing for the presence of MSAs and MAAs.
Muscle enzymes
Patients with IIM often have elevated levels of muscle enzymes in serum, indicating active muscle disease.1,4,5 An elevated level of any of the following enzymes is consistent with IIM: creatine kinase (test code 374), lactate dehydrogenase (test code 593), aspartate aminotransferase (test code 822), alanine aminotransferase (test code 823), and aldolase (test code 227).1,9 Creatine kinase is the most sensitive muscle enzyme1,5; patients with IIM often have creatine kinase levels up to 50 times the upper limit of normal (ULN), with the highest levels seen in immune-mediated necrotizing myopathy (IMNM, up to 100 times the ULN) and the lowest seen in inclusion body myositis (IBM, up to 10 times the ULN).5 However, not all patients with IIM have elevated muscle enzyme levels, especially those with IBM and amyopathic dermatomyositis.1
Autoantibodies
Consensus guidelines from the European Neuromuscular Centre (ENMC) include testing for MSAs and MAAs (Table 3) as part of an optimal testing strategy for suspected IIM.8 MSAs and MAAs are found in up to 80% of patients with IIM5 and are strongly associated with homogenous patient subgroups. MSAs are virtually 100% specific for IIM,6,7 and individual MSAs, which are usually mutually exclusive, are highly specific for certain IIM subtypes. MAAs are often found in IIM but are not specific for it6,7; they can also be found in other autoimmune rheumatic diseases and thus are associated with overlap myositis.1,6
Quest offers testing in accordance with the ENMC’s optimal testing strategy, which includes testing most MSAs.8 Quest’s MSA panels include the Extended Myositis Panel (test code 10257) and the Myositis Specific 11 Antibody Panel (test code 94777), which does not include cN-1A (test code 10266) or HMGCR (test code 39044) antibodies (available individually). Jo-1 antibody is also available individually (test code 5810).
If any autoantibody result is positive, further autoantibody testing may not be necessary, as patients rarely have more than 1 type of MSA (estimated prevalence, 0.11%).7,13 However, if all MSAs are negative, testing for MAAs may be appropriate. Quest offers individual tests for fibrillarin (U3 RNP, test code 34262), PM/Scl-100 (test code 94646), RNP (test code 19887), SS-A (test code 38568), and Sm/RNP (test code 38567). These and additional MAAs (Ku and PM/Scl-75) are available in the Interstitial Lung Disease panel (test code 39149), which includes 20 autoantibodies found in connective tissue diseases associated with interstitial lung disease.
The presence of an MSA or MAA is highly suggestive of IIM. Individual autoantibodies are highly specific for IIM subtypes and may be associated with certain clinical features, complications, and outcomes (Table 3).1,6,7 The absence of MSAs and MAAs does not rule out IIM, as up to 30% of patients with IIM do not have these autoantibodies.1 Some of these patients may have seronegative IMNM, which has no known autoantibody associations.1,4
Table 3. Clinical Significance of Autoantibodies in IIMs [return to contents]
| Autoantibody | Clinical associations1,2,4,6,7,10–12 |
IIM subtypea |
MSAs |
||
Jo-1 |
|
ASyS highly likely |
PL-7 |
|
|
PL-12 |
||
EJ |
|
|
OJ |
|
|
Mi-2α |
|
DM highly likely |
Mi-2β |
||
MDA-5 |
|
|
NXP-2 |
|
|
TIF1-γ |
|
|
cN-1A |
|
IBM likely |
SRP |
|
IMNM highly likely |
HMGCR |
|
|
MAAs |
||
Fibrillarin (U3 RNP) |
|
Overlap myositis likely |
Ku |
|
|
PM/Scl-75 |
|
|
PM/Scl-100 |
||
U1 RNP |
|
|
SS-A |
|
|
| ASyS, antisynthetase syndrome; cN-1A, cytosolic 5′-nucleotidase 1A; DM, dermatomyositis; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; IBM, inclusion body myositis; IIM, idiopathic inflammatory myopathy; ILD, interstitial lung disease; IMNM, immune-mediated necrotizing myopathy; MAA, myositis-associated autoantibody; MCTD, mixed connective tissue disease; MDA-5, melanoma differentiation-associated protein 5; MSA, myositis-specific autoantibody; NXP-2, nuclear matrix protein 2; RNP, ribonucleoprotein; SLE, systemic lupus erythematosus; SRP, signal recognition particle; SS, Sjögren syndrome; SSc, systemic sclerosis; SS-A, Sjögren syndrome antigen A; TIF1-γ, transcription intermediary factor 1 gamma. | |
| a | When clinical features are consistent. |
| b | Because of the rarity of these autoantibodies, clinical associations have not yet been established. |
| c | cN-1A is commonly considered an MSA but is not 100% specific for IIM.6,7 |
References [return to contents]
- Lundberg IE, Fujimoto M, Vencovsky J, et al. Idiopathic inflammatory myopathies. Nat Rev Dis Prim. 2021;7(1):86. doi:10.1038/s41572-021-00321-x
- Oldroyd AGS, Callen JP, Chinoy H, et al. International guideline for idiopathic inflammatory myopathy-associated cancer screening: an International Myositis Assessment and Clinical Studies Group (IMACS) initiative. Nat Rev Rheumatol. 2023;19(12):805-817. doi:10.1038/s41584-023-01045-w
- van Rilland EDZ, Yao L, Stevens KJ, et al. Myositis and its mimics: guideline updates, MRI characteristics, and new horizons. Am J Roentgenol. 2024;223(2):e2431359. doi:10.2214/ajr.24.31359
- Tsamis KI, Boutsoras C, Kaltsonoudis E, et al. Clinical features and diagnostic tools in idiopathic inflammatory myopathies. Crit Rev Clin Lab Sci. 2022;59(4):219-240. doi:10.1080/10408363.2021.2000584
- Dalakas MC. Chapter 18: Autoimmune inflammatory myopathies. In: Younger DS, ed. Motor System Disorders, Part I: Normal Physiology and Function and Neuromuscular Disorders. Vol 195. Handbook of Clinical Neurology. Elsevier; 2023:425-460. doi:10.1016/b978-0-323-98818-6.00023-6
- Ogawa-Momohara M, Muro Y. Myositis-specific and myositis-associated autoantibodies: their clinical characteristics and potential pathogenic roles. Immunol Med. 2024. doi:10.1080/25785826.2024.2413604
- Halilu F, Christopher-Stine L. Myositis-specific antibodies: overview and clinical utilization. Rheumatol Immunol Res. 2022;3(1):1-10. doi:10.2478/rir-2022-0001
- Damoiseaux J, Mammen AL, Piette Y, et al. 256th ENMC International Workshop: myositis specific and associated autoantibodies (MSA-ab), Amsterdam, The Netherlands, 8-10 October 2021. Neuromuscul Disord. 2022;32(7):594-608. doi:10.1016/j.nmd.2022.05.011
- 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;76(12):1955. doi:10.1136/annrheumdis-2017-211468
- Kwiatkowska D, Reich A. The significance of autoantibodies in juvenile dermatomyositis. BioMed Res Int. 2021;2021(1):551354. doi:10.1155/2021/5513544
- Salam S, Dimachkie MM, Hanna MG, et al. Diagnostic and prognostic value of anti-cN1A antibodies in inclusion body myositis. Clin Exp Rheumatol. 2022;40(2):384-393. doi:10.55563/clinexprheumatol/r625rm
- Satoh M, Ceribelli A, Hasegawa T, et al. Clinical Significance of Antinucleolar Antibodies: Biomarkers for Autoimmune Diseases, Malignancies, and others. Clin Rev Allergy Immunol. 2022;63(2):210-239. doi:10.1007/s12016-022-08931-3
- Lega JC, Fabien N, Reynaud Q, et al. The clinical phenotype associated with myositis-specific and associated autoantibodies: A meta-analysis revisiting the so-called antisynthetase syndrome. Autoimmun Rev. 2014;13(9):883-891. doi:10.1016/j.autrev.2014.03.004
Content reviewed 3/2025