Abstract
This cross-sectional study compares the positivity rates of all commonly tested myositis-specific autoantibodies, myositis-associated autoantibodies, and antinuclear antibody in classic dermatomyositis vs clinically amyopathic dermatomyositis.
Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) subclassified as classic DM (CDM) and clinically amyopathic DM (CADM) based on the presence or absence of clinically evident muscle disease. It can involve myositis-associated autoantibodies (MAA) and myositis-specific autoantibodies (MSA). The associations between MSA and specific DM phenotypes have been well studied but might not be fully captured by commercial autoantibody panels in clinical settings.1,2 To better understand the utility of autoantibody status in DM phenotyping, we compared the positivity rates of all commonly tested MSA, MAA, and antinuclear antibodies (ANA) in CDM vs CADM.
Methods
This cross-sectional study assessing the association between DM subtype and autoantibody positivity rate included adult patients with CDM and CADM seen at the University of Pennsylvania rheumatology-dermatology clinic who had myositis autoantibody testing between 2016 and 2024. This study followed the STROBE reporting guideline and was approved by the University of Pennsylvania Institutional Review Board. Participants provided written informed consent. We evaluated the presence of MAA, MSA, and ANA. An antibody was considered present if ever positive. Details on study dates, software used for analysis, and statistical assessment and significance are available in eMethods of Supplement 1.
Results
We identified 320 patients with DM (mean [SD] age of 53 [14] years; 276 female [86%], 44 male [14%]). Sixteen types of panels from 5 laboratories were recorded (Table 1).
Table 1. Testing Laboratories, Tested Antibodies, and Detection Assays of Myositis Autoantibody Panels Performed in the Study Cohort.
| Laboratory/panel name | No. (%) performed (n = 373) | Tested antibodies | Tested antibodies (for No. of tested antibodies <10) | Untested antibodies (for No. of tested antibodies ≥10) | Assay | |
|---|---|---|---|---|---|---|
| Type | No. | |||||
| ARUP | 191 (51) | Immunoblot, IP, multiplex bead assaya | ||||
| Myositis extended panel | 170 (46) | MSA, MAA | 16 | NA | Anti-U2-RNP | |
| Myositis antibody comprehensive | 11 (3) | MSA, MAA | 14 | NA | Antibodies to TIF-1γ, MDA-5, NXP-2, SAE | |
| Myositis-specific antibody | 5 (1) | MSA | 11 | NA | Antibodies to SSA, Pm-Scl, Ku, U1-RNP, U2-RNP, U3-RNP | |
| Polymyositis and dermatomyositis panel | 5 (1) | MSA | 11 | NA | Antibodies to SSA, Pm-Scl, Ku, U1-RNP, U2-RNP, U3-RNP | |
| Labcorp | 97 (26) | ELISA, RIPA gel radiographyb | ||||
| Myomarker 3 plus profile | 67 (18) | MSA, MAA | 17 | NA | NA | |
| Myositis panel III | 13 (3) | MSA, MAA | 11 | NA | Antibodies to TIF-1γ, MDA5, NXP-2, SAE, U2-RNP, U3-RNP | |
| Myositis panel VI | 7 (2) | MSA, MAA | 17 | NA | NA | |
| Myositis panel I | 4 (1) | MSA, MAA | 7 | Antibodies to Mi-2, SRP, PL-7, PL-12, EJ, OJ, Ku | NA | |
| Myositis panel II | 3 (1) | MSA, MAA | 7 | Antibodies to Mi-2, SRP, PL-7, PL-12, EJ, OJ, Ku | NA | |
| Myositis panel IV | 3 (1) | MSA, MAA | 8 | Antibodies to Mi-2, SRP, PL-7, PL-12, EJ, OJ, Ku, U1-RNP | NA | |
| Quest | 68 (18) | Chemiluminescence, ELISA, line blot | ||||
| Myositis-specific 11 antibody panel | 29 (8) | MSA | 10 | NA | Antibodies to SAE, SSA, Pm-Scl, Ku, U1-RNP, U2-RNP, U3-RNP | |
| Myositis panel comprehensive | 25 (7) | MSA | 6 | Antibodies to PL-7, PL-12, Mi-2, Jo-1, EJ, OJ | NA | |
| Extended myositis-specific antibody panel | 9 (2) | MSA | 12 | NA (includes anti-HMGCR, anti-cN-1A) | Antibodies to SAE, SSA, Pm-Scl, Ku, U1-RNP, U2-RNP, U3-RNP | |
| Myositis AssessR plus JO-1 | 5 (1) | MSA, MAA | 8 | Antibodies to Mi-2, SRP, PL-7, PL-12, EJ, OJ, Jo-1, Ku | NA | |
| OMRF | ||||||
| Myositis panel | 12 (3) | MSA, MAA | 12 | NA | Antibodies to TIF-1γ, MDA-5, NXP-2, SAE, U3-RNP | IP, ID, IF |
| Mayo | ||||||
| Myomarker panel 3 | 5 (1) | MSA, MAA | 10 | NA | Antibodies to TIF-1γ, MDA-5, NXP-2, Jo-1, SAE, Pm-Scl, SSA | ELISA, RIPA gel radiography |
Abbreviations: ARUP, Associated Regional and University Pathologists Inc; ELISA, enzyme-linked immunosorbent assay; ID, immunodiffusion; IF, immunofluorescence; IP, immunoprecipitation; MAA, myositis-associated autoantibodies; MDA-5, melanoma differentiation-associated protein 5; MSA, myositis-specific autoantibodies; NA, not applicable; NXP-2, nuclear matrix protein 2; OMRF, Oklahoma Medical Research Foundation; RIPA, radioimmunoprecipitation assay; SAE, small ubiquitin-like modifier activating enzyme; SRP, signal recognition particle; TIF-1γ, transcription intermediary factor 1 γ.
ARUP uses qualitative immunoblot for anti-MDA-5, anti-NXP-2, anti-SAE, anti-TIF-1γ, anti-PM/Scl-100, anti-RNPs; qualitative IP for anti-Mi-2, anti-TIF-1γ, anti-EJ, anti-OJ, anti-PL-7, anti-PL1-2, anti-SRP; and semiquantitative multiplex bead assay for anti-Jo-1, anti-SSA.
Labcorp uses ELISA for anti-MDA-5, anti-NXP-2, anti-SAE, anti-TIF-1γ, anti-PM/Scl-100, anti-Ku, anti-SSA, anti-U1-RNP, anti-Jo-1, anti-EJ, anti-OJ, anti-PL-7, anti-PL-12; and RIPA gel radiography for anti-Mi-2, anti-Jo-1, anti-EJ, anti-OJ, anti-PL-7, anti-PL-12, anti-SRP, anti-U2-RNP, anti-U3-RNP.
This cohort consisted of 198 (62%) patients with CDM and 122 (38%) patients with CADM, with a mean (SD) of 1.2 (0.5) panels performed per patient. MSA were positive in 47% of patients with CDM and 40% of patients with CADM (P = .20); MAA were positive in 29% of patients with CDM and 26% of patients with CADM (P = .65) (Table 2). Similar results were found in patients tested by the most comprehensive panels that assessed 17 autoantibodies (MSA: CDM 14/35 [40%], CADM 8/25 [32%]; P = .53; MAA: CDM 8/35 [23%], CADM 5/25 [20%]; P = .80). Within each laboratory, no statistically significant difference in MSA and MAA positivity rates was found between panels performed in patients with CDM and patients with CADM. In both subtypes, anti-TIF-1γ was the most common MSA and anti-SSA the most common MAA. ANA were positive in 63% of patients with CDM vs 49% of patients with CADM (P = .045). Among those with both negative MSA and MAA results, ANA were positive in 49% of patients with CDM and 36% of patients with CADM (P = .20).
Table 2. Positivity Rates of MSA, MAA, and ANA by DM Subtype.
| Positivity status | DM subtype, No./total No. (%) | P value | |
|---|---|---|---|
| Classic (n = 198) | Clinically amyopathic (n = 122) | ||
| Any MSA positive | 94/198 (47) | 49/122 (40) | .20 |
| Any MAA positive | 48/168 (29) | 26/100 (26) | .65 |
| Any ANA positive | 90/143 (63) | 42/85 (49) | .045 |
| Either MSA or MAA positive | 118/198 (60) | 63/122 (52) | .16 |
| Both MSA and MAA negative | 80/198 (40) | 59/122 (48) | .16 |
| Both MSA and MAA negative but ANA positive | 26/53 (49) | 13/36 (36) | .23 |
| MSA | |||
| Anti-TIF-1γ | 29/169 (17) | 21/97 (22) | .37 |
| Anti-MDA-5 | 13/166 (8) | 10/97 (10) | .49 |
| Anti-NXP-2 | 16/162 (10) | 5/94 (5) | .20 |
| Anti-SAE | 10/137 (7) | 7/79 (9) | .68 |
| Anti-Mi-2 | 12/197 (6) | 6/119 (5) | .70 |
| Anti-PL-7 | 10/197 (5) | 2/119 (2) | .22 |
| Anti-Jo-1 | 9/192 (5) | 1/118 (1) | .10 |
| Anti-SRP | 3/187 (2) | 3/109 (3) | .67 |
| Anti-PL-12 | 2/197 (1) | 1/119 (1) | >.99 |
| Anti-OJ | 1/197 (1) | 1/119 (1) | >.99 |
| Anti-EJ | 0 | 0 | >.99 |
| MAA | |||
| Anti-SSA | 33/159 (21) | 18/94 (19) | .76 |
| Anti-SSA-52 | 26/159 (16) | 15/94 (16) | .93 |
| Anti-SSA-60 | 11/159 (7) | 6/94 (6) | .89 |
| Anti-SSA-52 positive with CT-proven ILDa | 11/26 (42) | 5/15 (33) | .57 |
| Anti-Pm-Scl | 13/160 (8) | 5/94 (5) | .40 |
| Anti-U1-RNP | 12/160 (8) | 3/93 (3) | .27 |
| Anti-Ku | 1/166 (1) | 3/100 (3) | >.99 |
| Anti-U2-RNP | 0 | 1/57 (2) | .39 |
| Anti-U3-RNP | 2/139 (1) | 1/84 (1) | >.99 |
| ANA | |||
| Anti-RNP | 5/42 (12) | 1/20 (5) | .65 |
| Anti-Smith | 0 | 0 | >.99 |
Abbreviations: ANA, anti-nuclear autoantibodies; DM, dermatomyositis; ILD, interstitial lung disease; MAA, myositis-associated autoantibodies; MDA-5, melanoma differentiation-associated protein 5; MSA, myositis-specific autoantibodies; NXP-2, nuclear matrix protein 2; SAE, small ubiquitin-like modifier activating enzyme; SRP, signal recognition particle; TIF-1γ, transcription intermediary factor 1 γ.
Consistent with the known association between anti-SSA-52 and higher frequency of interstitial lung disease (ILD), 39% anti-SSA-52-positive patients vs 19% anti-SSA-52-negative patients developed CT-proven ILD; P = .005.
Discussion
We observed no significant difference in MSA and MAA prevalence between CDM and CADM on commercial autoantibody testing. MSA were previously reported in over 50% patients with IIM,3 slightly higher than the prevalence in this DM-only cohort. MAA prevalence reached 35% to 40% in other cohorts compared with 26% to 29% in ours.4 Besides population characteristics, such discrepancies might be due to the inconsistency of detection methods and tested autoantibodies.
In this cohort study, ANA were significantly more common in patients with CDM, which suggests a potential association between ANA positivity and DM muscle involvement that merits further investigation. More than one-third of patients with negative results for MSA and MAA had positive results for ANA, suggesting the presence of undiscovered DM-related autoantibodies.
Although DM autoantibody profile may be a helpful tool in prognosis when positive, its utility is limited by the variability in detection methods and tested antibodies. Hence, we need to refine and standardize myositis-related autoantibody testing in DM, which remains a clinical diagnosis.
eMethods. Study Dates, Software Used for Analysis, and Statistical Assessment and Significance
Data Sharing Statement
References
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Supplementary Materials
eMethods. Study Dates, Software Used for Analysis, and Statistical Assessment and Significance
Data Sharing Statement
