Myositis-Associated Autoantibodies in Patients With Juvenile Myositis Are Associated With Refractory Disease and Mortality

Abstract

Objective: Myositis-associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain largely uncharacterized in patients with juvenile-onset myositis. Moreover, it is unknown whether the number of MAAs is associated with disease severity.

Methods: Patients with juvenile myositis in cross-sectional natural history studies who underwent testing for myositis autoantibodies were included. Demographics, myositis autoantibodies, clinical characteristics, medications received, and outcomes of those with and without MAAs were compared. Multivariable logistic regression was performed to determine whether the number of MAAs detected was associated with severe disease features.

Results: Among 551 patients, 36% had an MAA and 13% had more than one MAA. Among those who were MAA positive, there was a higher frequency of overlap myositis (18% vs 5.9%, P < 0.001). MAA positivity was associated with certain clinical features, including Raynaud phenomenon (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.41-4.28) and ILD (OR 3.43, 95% CI 1.75-6.96), as well as a chronic disease course (OR 1.72, 95% CI 1.10-2.72) and mortality (OR 3.76, 95% CI 1.72-8.43). The number of MAAs was also associated with mortality (OR 1.83, 95% CI 1.16-2.86).

Conclusion: MAAs were prevalent in a large cohort of patients with juvenile myositis. ILD, refractory disease, and mortality were associated with MAA positivity. Prospective studies are needed to determine whether early detection of MAAs may lead to improved outcomes for patients with juvenile myositis.

Figure 1.. Myositis-associated autoantibodies occur across myositis-specific autoantibody serologic subgroups and in combination

A) Breakdown of MAAs across serologic subgroups. MAAs are represented by the colors indicated in the legend. MSAs are displayed on the x-axis. The count for each MAA within a particular MSA subgroup is displayed along the y-axis. For some patients, more than one MAA was present. Anti-SAE (1 patient with anti-Ro52 Abs) is not shown. B) Combinatorial expression of MAAs. The count for each MAA is displayed by the horizontal bars. The count for each combination of MAAs is displayed by the vertical bars. In the matrix, gray circles represent the absence of an MAA, black circles denote the presence of an MAA, and the connecting black lines denote multiple MAAs present in combination. Abbreviations: Ab, autoantibody; ARS, aminoacyl-tRNA synthetase; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; MAA, myositis-associated autoantibody; MDA5, melanoma differentiation associated protein 5; MSA, myositis-specific autoantibody; NT5C1A, cytosolic 5’-nucleotidase 1A; NXP2, nuclear matrix protein 2; PM/Scl, polymyositis/scleroderma; RNP, ribonucleoprotein; SAE, small ubiquitin-like modifier activating enzyme; SRP, signal recognition particle; TIF-1, transcription intermediary factor 1; TMG, trimethylguanosine.

Figure 2.. Clinical associations of myositis-associated autoantibodies

Forest plot of multivariable logistic regression results for predictor variables that were associated with MAA positivity in univariable analyses. Predictor variables are along the Y axis. Odds ratios are along the X axis. A) Clinical features. B) Treatments and outcomes. Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; CK, creatine kinase; DMARD, disease-modifying antirheumatic drug; IVIG, intravenous immunoglobulin; IVMP, intravenous methylprednisolone; LDH, lactate dehydrogenase; MAA, myositis-associated autoantibody.

Figure 3.. Clinical associations of anti-Ro60 autoantibodies

Forest plot of multivariable logistic regression results for predictor variables that were associated with positivity for anti-Ro60 autoantibodies in univariable analyses. Predictor variables are along the Y axis. Odds ratios are along the X axis. A) Clinical features. B) Treatments and outcomes. Abbreviations: DMARD, disease-modifying antirheumatic drug; IVIG, intravenous immunoglobulin; IVMP, intravenous methylprednisolone.

Figure 4.. Clinical associations of anti-U1-RNP autoantibodies

Forest plot of multivariable logistic regression results for predictor variables that were associated with positivity for anti-U1-RNP autoantibodies in univariable analyses. Predictor variables are along the Y axis. Odds ratios are along the X axis. Abbreviations: EKG, electrocardiogram.

Figure 5.. Clinical associations of anti-PM/Scl autoantibodies

Forest plot of multivariable logistic regression results for predictor variables that were associated with positivity for anti-PM/Scl autoantibodies in univariable analyses. Predictor variables are along the Y axis. Odds ratios are along the X axis. Abbreviations: CK, creatine kinase; IVMP, intravenous methylprednisolone.