ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1297

Increased Hsp90 in Plasma and Muscle Tissue Associates with Disease Activity and Skeletal Muscle Involvement in Idiopathic Inflammatory Myopathies

Hana Storkanova1, Sabina Oreska 2, Maja Spiritovic 3, Barbora Hermankova 4, Olga Kryštůfková 1, Herman Mann 2, Martin Komarc 5, Josef Zamecnik 6, Karel Pavelka 2, Jiri Vencovsky 1, Ladislav Senolt 2 and Michal Tomcik 2, 1Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Prague, Czech Republic, Prague, Czech Republic, 2Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Prague, Czech Republic, Prague 2, Czech Republic, 3Faculty of Physical Education and Sport, Department of Physiotherapy, Charles University, Prague, Czech Republic, Prague 2, Hlavni mesto Praha, Czech Republic, 4Faculty of Physical Education and Sport, Department of Physiotherapy, Charles University, Prague, Czech Republic, Prague, Czech Republic, 5Department of Methodology, Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic, Prague, Czech Republic, 65Department of Pathology and Molecular Medicine, 2nd Medical School and University Hospital Motol, Charles University, Prague, Czech Republic, Prague, Czech Republic

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ,

Session Information

Date: Monday, November 11, 2019

Title: Muscle Biology, Myositis & Myopathies Poster II

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Heat shock proteins (Hsps) are chaperones playing important roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells.

The aim of our study was to assess Hsp90 expression in muscle biopsies and plasma of patients with idiopathic inflammatory myopathies (IIM) and to characterize its association with IIM-related features.

Methods: Total of 277 patients with IIM (198 females; mean age 54.8; disease duration 4.1 years; dermatomyositis (DM, 104)/polymyositis (PM, 108)/cancer associated myositis (CAM, 31)/ necrotizing myopathy (IMNM, 25) and 157 healthy individuals (92 females; mean age  47.0) were included in plasma analysis.  Muscle biopsy samples (PM, DM, IMNM, myodystrophy, myasthenia gravis) were stained for Hsp90α (Thermo Fisher Scientific, USA) and Hsp90β (Abcam, UK). Plasma Hsp90 was measured by ELISA kit (eBioscience, Vienna, Austria). The cytokines were performed using Bio-Plex ProTM human Cytokine 27-plex Assay (BIO-RAD, California, USA .Data are presented as median.

Results: In muscle biopsies, Hsp90 expression of both subunits was higher in IIM than in controls. Increased Hsp90 was detected in perifascicular degenerating and regenerating fibers, inflammatory cells (DM, PM), and necrotic and regenerating fibers (IMNM). Plasma Hsp90 levels were increased in IIM patients compared to healthy controls (p< 0.0001), and in individual subgroups of IIM vs. healthy controls (p< 0.0001 for all) (Tab1). When adjusted for age and sex, these differences remained still significant (p< 0.0001). Hsp90 was higher in males compared to females (p=0.040) and in patients with ILD (p=0.003), with cardiac involvement (p=0.004), with dysphagia (p=0.018) and with presence of anti-Ro52 autoantibodies (p=0.036) (Tab2). Hsp90 levels in all patients positively correlated with muscle enzymes (Tab.3). Increased Hsp90 was associated with disease activity and skeletal muscle involvement (Tab.3). Interestingly, out of all clinical parameters listed in above-mentioned univariate analysis, in multiple regression analysis Hsp90 levels in IIM patients were significantly affected by muscle enzymes only (p< 0.0001, β=0.345). Furthermore, Hsp90 positively correlated with some crucial cytokines involved in pathogenesis of myositis (Tab.3).

Tab.1

Characteristics

median (IQR)

ZK

9.76 (7.5 – 13.8)

IZM

55.9 (46.9 – 62.5)

DM

22.0 (14.1 – 41.2)

PM

19.7 (14.3 – 42.2)

CAM

18.9 (11.7 – 29.7)

IMNM

19.6 (16.3 – 45.5)

Tab.2

Clinical parameters

(+) median (IQR)

(-) median (IQR)

Gender (+ female/ – male)

19.6 (13.4 – 35.6)

25.3 (15.6 – 50.0)

+ ILD / -ILD

25.4 (15.5 – 50.7)

18.9 (12.8 – 30.3)

+ CI / – CI

27.5 (18.1 – 51.5)

19.3 (13.3 – 39.3)

+ dysphagia / – dysphagia

25.0 (15.9 – 50.0)

18.2 (13.4 – 34.3)

+ Ro52 / – Ro52

29.5 (55.4 – 15.5)

19.2 (13.9 – 31.5)

Conclusion: We demonstrate increased Hsp90 expression in IIM muscle biopsy samples, specifically in inflammatory cells, degenerating, regenerating and/or necrotic fibers. Increased Hsp90 plasma levels in IIM patients are associated with disease activity and damage, and with the involvement of proximal skeletal muscles, heart and lungs.

 

Acknowledgement: Supported by AZV-16-33542A, MHCR 023728 and SVV – 260373.

Disclosure: H. Storkanova, None; S. Oreska, None; M. Spiritovic, None; B. Hermankova, None; O. Kryštůfková, None; H. Mann, None; M. Komarc, None; J. Zamecnik, None; K. Pavelka, AbbVie, 8, Abbvie, 5, 8, Amgen, 5, 8, BMS, 8, Egis, 5, 8, Lilly, 5, 8, MSD, 8, Novartis, 5, 8, Pfizer, 5, 8, Roche, 5, 8, UCB, 8; J. Vencovsky, None; L. Senolt, None; M. Tomcik, None.

To cite this abstract in AMA style:

Storkanova H, Oreska S, Spiritovic M, Hermankova B, Kryštůfková O, Mann H, Komarc M, Zamecnik J, Pavelka K, Vencovsky J, Senolt L, Tomcik M. Increased Hsp90 in Plasma and Muscle Tissue Associates with Disease Activity and Skeletal Muscle Involvement in Idiopathic Inflammatory Myopathies [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/increased-hsp90-in-plasma-and-muscle-tissue-associates-with-disease-activity-and-skeletal-muscle-involvement-in-idiopathic-inflammatory-myopathies/. Accessed .

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