THU0080 Serum irisin and myostatin levels in patients with rheumatoid arthritis

Abstract

BackgroundRheumatoid arthritis (RA) patients have loss of muscle mass. The balance between muscle protein synthesis and degradation is regulated by cytokines and growth factors, named myokines, such as irisin and myostatin. Myokines are mainly expressed by skeletal muscle and exert systemic effects promoting crosstalk among different tissues. Irisin increases cortical bone mass and its low levels are related to muscle atrophy and obesity[,1, 2 while myostatin is a negative regulator of muscle growth and regeneration and has a direct role in osteoclastogenesis of inflammatory bone destruction[.3, 4 ObjectivesTo evaluate serum levels of irisin and myostatin and body composition of RA patients and controls.Methods122 female patients with RA, mean age 53 years, mean disease activity score (DAS28) 4.09, mean disease duration 11.2 years and mean body mass index 27.33 kg/m2 were included. 69 age and sex-matched healthy subjects were enrolled as control group. Irisin (Phoenix Pharmaceuticals) and myostatin (R and D Systems) serum levels were evaluated by ELISA. Fat mass index (FMI;Kg/m2) and appendicular lean mass index (ALMI;Kg/m2) were assessed by total body dual-energy x-ray absorptiometry. Student’s t test and Spearman correlation were performed. Significance was set at p<0.05.Table 1Irisin and myostatin serum levels of RA patients and controlsnIrisin (mean±SD)Myostatin (mean±SD) RA patients treated with biologics1331,71±7,69#2448,64±1114,90*#RA patients non-treated with biologics2725,93±6,893261,66±1156,28+Controls3030,36±10,954049,08±1610,01*p<0,05 RA patients treated with biologics vs controls; #p<0,05 RA patients treated with biologics vs RA patients non-treated with biologics;+p<0,05 RA patients non-treated with biologics vs controls.ResultsRA patients had decreased serum levels of irisin (25,61±8,25 vs 30,36±10,95 ng/ml; p<0.05) and myostatin (3011,28±1271,11 vs 4049,08±1610,01 pg/ml; p<0.05), decreased ALMI (6,09±0,88 vs 6,50±1,10; p<0.05) and increased FMI (11,26±3,30 vs 9,44±2,65; p<0.05), compared to controls. No correlations were observed among irisin and myostatin levels and ALMI and FMI. Of the 122 RA patients, 40 were analysed for the use of biologic medication. Serum levels of irisin and myostatin were different between RA patients treated and non-treated with biologics (table 1).ConclusionsRA patients presented loss of lean mass and gain of fat mass, as well as lower irisin and myostatin serum levels, in comparison with controls. Additionally, the use of biologic medication by patients impacted on myokines serum levels. Further analyses are needed for a better comprehension of irisin and myostatin roles in RA, and to verify their correlation to other RA features.References[1] Colaianni G, et al. Proc Natl Acad Sci2015;112(39):12157–62.[2] Chang J, et al. Geriatr Gerontol Int. 2017;17(11):2266–2273.[3] Huang Z, et al. Cell Signal2011;23(9):1441–6.[4] Dankbar B, et al. Nat Med2015;21(9):1085–90.Disclosure of InterestNone declared

Myostatin Levels and the Risk of Myopenia and Rheumatoid Cachexia in Women with Rheumatoid Arthritis

“…Regarding the high levels of myostatin, we identified that approximately one-third of these RA patients had high serum levels of myostatin compared to only 4% of the controls. Contrary to these results, Silva et al, in a published abstract, reported lower myostatin levels in RA patients than in controls [ 12 ]. However, the difference between the results of both studies cannot be explained yet because, to date, the results of Silva's study have not been published in their entirety.…”

“…These associations between increased myostatin and myopenia have also been reported in men from healthy community-living older adults, supporting our findings [ 41 , 42 ]. Only a few studies have been conducted in RA patients to assess this association [ 11 , 12 ]. The first study was published as abstract by Silva et al [ 12 ].…”

“…Only a few studies have been conducted in RA patients to assess this association [ 11 , 12 ]. The first study was published as abstract by Silva et al [ 12 ]. Silva et al studied 122 females with RA and 30 subjects without rheumatic diseases and found no correlations between the myostatin levels and low muscle mass (assessed by the appendicular lean mass index measured by DXA) or between the severity of disease activity in RA (DAS28-ESR) and myostatin levels [ 12 ].…”

“…To date, there is growing interest from physicians and researchers regarding the effects of myostatin on skeletal muscle in patients with chronic diseases. Regarding RA, some works have investigated the relationship of myostatin with some relevant clinical variables [ 10 – 12 ]. Recently, we identified a relationship between high serum concentrations of myostatin and an increase in joint inflammation as well as a decrease in skeletal muscle mass in patients with RA [ 10 ].…”

“…However, that study had an insufficient sample size to evaluate whether a cut-off value for high myostatin levels could help to identify myopenia or to demonstrate an increase in the risk of rheumatoid cachexia [ 10 ]. To date, the relevance of elevated levels of this myokine in the myopenia observed in RA patients has not been proven, and some authors have reported conflicting results, making it difficult to determine the clinical value of serum myostatin; for example, Wada et al observed that lower myostatin levels were associated with myopenia in patients with RA [ 11 ], while in an abstract published by Silva et al, there was no correlation found between myostatin concentrations and the quantity of appendicular lean mass or the fat mass indices [ 12 ]. However, the results of both studies contradict the experimental evidence regarding the effect of myostatin on regulating the growth of skeletal myocytes decreasing the number and size of muscle fibers [ 8 ].…”