Background/Purpose: Heat shock proteins (Hsps) are chaperones playing important roles in skeletal muscle physiology, adaptation to exercise or stress, and in activation of inflammatory cells. Hsp90 expression was shown to be increased in regenerating and atrophic muscle fibers, and in macrophages and cytotoxic T-cells actively invading nonnecrotic muscle fibers in polymyositis. The aim of our study was to assess plasma Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and to characterize its association with IIM-related features.

Methods: A total of 277 patients with IIM (198 females, 79 males; mean age 54.8; disease duration 4.1 years; dermatomyositis (DM, 104)/polymyositis (PM, 104)/cancer associated myositis (CAM, 42)/ necrotizing myopathy (IMNM, 27)) and 100 age-/sex-matched healthy individuals were included. Patients with PM/DM fulfilled Bohan and Peter diagnostic criteria and CAM was defined as cancer occurring within 3 years of the diagnosis of myositis. Plasma Hsp90 levels were measured by ELISA (eBioscience, Vienna, Austria). Clinical disease circumstances were evaluated by Myositis Disease Activity Assessment (MYOACT), Myositis Intention to Treat Index (MITAX), Myositis Damage Index (MDI), physician and patient global activity using visual analogue scales (VAS) and manual muscle testing (MMT8). Levels of CK, LD, ALT, ASTand CRP were analyzed by routine laboratory techniques and IIM-associated autoantibodies by immunoprecipitation.  Data are presented as median (IQR).

Results: Plasma Hsp90 levels were increased in IIM patients compared to healthy controls (20.2 (14.3-40.1) vs. 9.2 (7.2-12.6) ng/ml, p < 0.0001), and between individual subgroups of IIM and healthy controls (PM: 19.4 (14.5-40.4), DM: 22.4 (14.3-43.5), CAM: 19.1 (12.3-29.8), IMNM: 19.6 (15.7-50.0) ng/ml, p < 0.0001 for all). Hsp90 levels in all patients positively correlated with LD and AST (r=0.551, p < 0.0001; r=0.372, p < 0.0001, respectively), and there was a trend towards correlation with CK (r=0.111, p=0.068). Increased Hsp90 was associated with decreased MMT8 values (r=-0.136, p=0.029), in particular with proximal muscles. Hsp90 positively correlated with patient and doctor disease activity (r=0.222, p=0.0004; r=0.217, p=0.0005, respectively), pulmonary and muscle disease activity (r=0.201, p=0.001; r=0.146, p=0.018, respectively), MITAX and MYOACT (r=0.175, p=0.005; r=0.159, p=0.012, respectively), and with MDI extent/severity (r=0.215, p=0.003; r=0.120, p=0.041, respectively). Higher Hsp90 was found in patients with IIM-associated interstitial lung disease, cardiac involvement and dysphagia (25.4 vs. 18.9, p=0.004; 27.5 vs. 19.3, p=0.004; 25.0 vs. 18.2, p=0.018, respectively). Increased Hsp90 was associated with higher prednisone equivalent dose (r=0.180, p=0.007) and treatment with DMARDs (22.0 vs. 18.9, p=0.013).

Conclusion: We demonstrate increased Hsp90 plasma levels in IIM patients that are associated with disease activity and damage, and with the involvement of proximal skeletal muscles, the heart and lungs. Hsp90 might become a useful biomarker of disease activity and muscle involvement in IIM.

Acknowledgement: Supported by BT Cure and MHCR 023728.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-levels-of-heat-shock-protein-90-are-increased-in-idiopathic-inflammatory-myopathies-and-correlate-with-disease-activity-skeletal-muscle-heart-and-lung-involvement/