Background/Purpose: Idiopathic inflammatory myositis (IIM) are rare and heterogenous. Myositis specific antibodies (MSA) show mutual exclusivity and identify specific clinical phenotypes¹. Most biomarker studies are limited by the number of patients of individual phenotypes. Since serum metabolomics can distinguish active from inactive myositis^2,3, we determined if the serum metabolomic profile is distinctive in clinical and antibody-based phenotypes.

Methods: Sera (n=116) from IIM (ACR-EULAR criteria, 34 years (23.5 – 50.5 IQR), M/F 28:88] were compared with healthy controls [n=18, age= 44 (35-50) years, M/F-8:10]. Clinical phenotypes were defined as previously described⁴ and antibody by presence of MSA and MAAs. In addition, those with 3 of 5 ASSD features were labelled as clinical ASSD for analysis.

Metabolic profiles were obtained at 800 MHZ NMR spectrometer and compared using multivariate partial least-squares discriminant analysis (PLS-DA). The discriminatory metabolites were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (p-value < 0.05). Metaboanalyst® was used for analysis.

Results: Serum metabolites were no different based on clinical diagnosis (Figure 1a) or in those with ILD, arthritis, bulbar weakness, amyopathic presentation and skin rashes (Gottron’s, heliotrope, mechanic’s hands, cutaneous ulcers and photosensitivity,) than individuals without these (Figure 1b-e). IIM with a clinical ASSD without ARS was similar to ARS group (Figure 1f). Metabolome clusters defined by distinct MSAs also exhibited significant overlap (Figure 2a-e). The presence and absence of MAA (Figure 2f) and ANA (Figure 2b) were not discriminative in the metabolome.

Conclusion: Serum metabolome does not reflect change with clinico-serologic phenotype in IIM, suggesting distinctive value as biomarker of disease activity uninfluenced by heterogeneity.

References

1. Gupta L, Gaur P, Agarwal V on behalf of -, et alSAT0323 MYOSITIS-SPECIFIC AND MYOSITIS-ASSOCIATED AUTOANTIBODIES IN A LARGE INDIAN COHORT OF INFLAMMATORY MYOSITIS REVEAL NOVEL CLINICO-PHENOTYPIC PATTERNSAnnals of the Rheumatic Diseases 2020;79:1107.
2. Gupta L, Kumar D, Kumar U, Guleria A, Zanwar A, Raj R, Misra R. NMR-Based Serum, Urine and Muscle Metabolomics in Inflammatory Myositis for Diagnosis and Activity Assessment: Serum Metabolomics Can Differentiate Active from Inactive Myositis [abstract]. Arthritis Rheumatol.2019; 71 (suppl 10). https://acrabstracts.org/abstract/nmr-based-serum-urine-and-muscle-metabolomics-in-inflammatory-myositis-for-diagnosis-and-activity-assessment-serum-metabolomics-can-differentiate-active-from-inactive-myositis/. Accessed June 14, 2020.
3. Chung YL, Rider LG, Bell JD, et al. Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies. Arthritis Rheum. 2005;53(4):565‐570. doi:10.1002/art.21331
4. Gupta L, Appani S, Janardana R, Muhammed H, Lawrence A, Amin S, et al. Meeting report: MyoIN – Pan-India collaborative network for myositis research. Indian J Rheumatol. 2019;14(2):136.

Figure 1. PLS-DA on Clinical Clusters of IIM

Figure 2. PLS-DA on Antibody Based Clusters of IIM

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