Plasma Myokine Profiles in Patients With AChR- and MuSK-Ab-Positive Myasthenia Gravis

Abstract

Background and purpose: Myokines include cytokines secreted by muscle fibers, which are the final targets of myasthenia gravis (MG). This pilot study investigated whether myokine plasma concentrations are altered in patients with MG and assessed the association between the concentration of each myokine and disease severity.

Methods: We compared the plasma concentrations of 15 myokines in 63 patients with acetylcholine receptor antibody (Ab)-positive MG and 14 with muscle-specific tyrosine kinase Ab-positive MG (MuSK MG) with those in 15 healthy controls. Plasma myokine concentrations were measured using a Luminex multiplex assay kit with magnetic beads that contained Abs for 15 myokines. Correlations between myokine concentration and clinical scale results were analyzed.

Results: The concentration of fractalkine in plasma was higher in MG (median [interquartile range]=419.6 [38.7-732.5] pg/mL) than in controls (158.5 [0.0-313.2] pg/mL, p=0.034). The leukemia inhibitory factor concentration was also found to be higher in MuSK MG (29.9 [8.7-40.1] pg/mL) than in healthy controls (7.6 [0.0-15.6] pg/mL, p=0.013). Fatty-acid-binding protein 3 (FABP3) concentrations in plasma were positively associated with clinical parameters for MG severity, including scores on the Quantitative Myasthenia Gravis score (p=0.008), Myasthenia Gravis Activities of Daily Living (p=0.003), and Myasthenia Gravis Composite (p=0.024) scales. FABP3 concentration in plasma tended to decrease after treatment in patients without additional relapse but increased in those with further relapse.

Conclusions: The plasma myokine profile was significantly altered in patients with MG. FABP3 concentration may be useful in assessing disease severity and predicting the treatment response.

Keywords: cytokine; myasthenia gravis; myokine.

Fig. 1. Comparison of plasma myokine concentrations between patients with myasthenia gravis who did and did not undergo thymectomy. Concentrations of erythropoietin (p=0.006), FGF21 (p=0.001), fractalkine (p=0.008), LIF (p=0.022), myostatin (p=0.007), oncostatin (p=0.016), and osteocrin (p=0.013) were significantly lower in patients who had undergone thymectomy. Circles denote outliers and asterisks denote extreme outliers. FGF21, fibroblast growth factor 21; LIF, leukemia inhibitory factor.

Fig. 2. Association between the FABP3 concentration in plasma and disease severity. Plasma FABP3 concentrations presented significant positive associations with scores on the (A) QMG, (B) MG ADL, and (C) MG Composite scales at the time of sampling. ADL, Activity of Daily Living; FABP3, fatty-acid-binding protein 3; MG, myasthenia gravis; QMG, Quantitative MG.

Fig. 3. Associations between FABP3 concentration in plasma and MGFA clinical classification at the time of sampling. FABP3 concentration tended to increase with the MGFA classification. FABP3, fatty-acid-binding protein 3; MGFA, Myasthenia Gravis Foundation of America.

Fig. 4. Changes in FABP3 concentration in plasma before and after treatment in patients with myasthenia gravis. (A) FABP3 concentration tended to decrease after treatment in patients who did not experience additional relapse (p=0.139) and (B) increased in patients who did experience further relapse (p=0.047). FABP3, fatty-acid-binding protein 3.