BACKGROUND: Heat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features. METHODS: Hsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay. RESULTS: Hsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3-40.1] vs 9.8 [7.5-13.8] ng/mL, p<0.0001). Elevated Hsp90 was found in IIM patients with pulmonary, cardiac, esophageal, and skeletal muscle involvement, with higher disease activity or damage, and with elevated muscle enzymes and crucial cytokines/chemokines involved in the pathogenesis of myositis (p<0.05 for all). Plasma Hsp90 decreased upon pharmacological treatment in both patients with early and established disease. Notably, Hsp90 plasma levels were slightly superior to traditional biomarkers, such as C-reactive protein and creatine kinase, in differentiating IIM from HC, and IIM patients with cardiac involvement and interstitial lung disease from those without these manifestations. CONCLUSIONS: Hsp90 is increased systemically in patients with IIM. Plasma Hsp90 could become an attractive soluble biomarker of disease activity and damage and a potential predictor of treatment response in IIM.

• Klíčová slova
• disease activity, disease damage, heat shock protein 90, idiopathic inflammatory myopathies, response to treatment, skeletal muscle involvement,
• MeSH
• biologické markery krev   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• kosterní svaly patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• myozitida krev   diagnóza   MeSH
• proteiny tepelného šoku HSP90 krev   MeSH
• průřezové studie MeSH
• regresní analýza MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• proteiny tepelného šoku HSP90 MeSH

Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dermatitida metabolismus   MeSH
• difuzní kapacita plic účinky léků   MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• intersticiální plicní nemoci krev   farmakoterapie   etiologie   MeSH
• kůže patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• oxid uhelnatý metabolismus   MeSH
• plíce patofyziologie   MeSH
• prospektivní studie MeSH
• proteiny tepelného šoku HSP90 krev   MeSH
• průřezové studie MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• systémová sklerodermie krev   komplikace   farmakoterapie   MeSH
• vitální kapacita účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• C-reaktivní protein MeSH
• cyklofosfamid MeSH
• imunosupresiva MeSH
• oxid uhelnatý MeSH
• proteiny tepelného šoku HSP90 MeSH