Background/Purpose: Altered body composition is a common feature of patients with rheumatoid arthritis (RA), up to two-thirds of affected patients showing loss of muscle mass and strength and a concomitant increase in fat mass, so-called “rheumatoid cachexia”. Despite great advances in the treatment of RA, such as biological agents and small-molecule compounds, rheumatoid cachexia persists even after joint inflammation has improved. Myostatin, a member of the transforming growth factor-beta superfamily, is a potent negative regulator of skeletal muscle growth and its inactivation can induce skeletal muscle hypertrophy, whereas its overexpression or systemic administration causes muscle atrophy. As it enhances proteolysis and inhibits protein synthesis in skeletal muscle, it has generated considerable interest as a potential regulator of cachexic status in patients with conditions such as cancers, cardiac failure, and HIV infection. In this study, we investigated the possible role of myostatin in body composition alteration in patients with RA.

Methods: This was a cross-sectional study. Ninety-six RA patients who visited Niigata University Hospital between April and June 2017 were recruited. Body composition in each subject was measured by bioelectrical impedance analysis with a tetrapolar impedance meter (InBody S-10, InBody Japan Inc., Tokyo, Japan). The serum myostatin level was measured by enzyme-linked immunosorbent assay with a commercially available kit (Quantikine ELISA GDF-8/Myostatin Immunoassay, R&D Systems, MN, USA). Patients’ laboratory findings and disease activities were also measured, and the correlations between the titer of serum myostatin and these factors were analyzed by Spearman’s correlation coefficient and stepwise multiple regression. In addition, 70 female patients from the cohort were divided into two groups according to their fat-free mass index (FFMI) (low FFMI group (FFMI< 13.82, n=20) and normal FFMI group (n=50)), and their clinical findings and serum myostatin levels were compared by Mann-Whitney U test. Differences at p < 0.05 were considered to be statistically significant.

Results: Spearman’s correlation coefficient analysis showed that the serum myostatin level was positively correlated with skeletal muscle mass index and FFMI, and negatively correlated with percentage body fat (%BF), fat mass index (FMI), the swollen joint count, ESR, and DAS28(4)-ESR. Stepwise multiple regression analysis selected FFMI as a positive independent variable (rho=0.3620, p=0.00019) and DAS28(4)-ESR as a negative independent variable (rho=-0.2298, p=0.0154) against the serum myostatin level, respectively. In these 70 female patients, %BF and FMI/FFMI ratio were significantly higher in the low FFMI group than in the normal FFMI group.

Conclusion: The serum myostatin level was significantly correlated with body composition and disease activity in patients with RA. Patients with a lower level of myostatin showed a tendency to have decreased skeletal muscle and increased body fat, suggesting that serum myostatin could be a possible biomarker of rheumatoid cachexia.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-myostatin-in-patients-with-rheumatoid-arthritis-and-its-correlations-with-body-compositions-and-the-disease-activity/