Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy

Figures

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  Fig. 1. Correlations between serum cytokine levels and clinical scores in FSHD1. Heat maps of Spearman’s correlation coefficient (Spearman R) and False Discovery Rate (FDR) using Benjamini and Hochberg method for cytokines and clinical scores in all patients (a.), males (b.), and females (c.).

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  Fig. 2. Correlations between serum IL-6 levels and clinical scores in FSHD1. Scatter plot representations of serum IL-6 levels versus MMT sum score (a.), Brooke score (b.), Vignos score (c.), clinical severity score (CSS) (d.), and age-corrected CSS (e.) in all patients, males, and females. Spearman R coefficients and p-values are indicated.

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  Fig. 3. Comparison of serum IL-6 levels with clinical severity in FSHD1 and with control. a. Scatter plot representation of serum IL-6 levels in the different groups according to clinical severity. A significant difference in serum IL-6 levels was obtained between patients with a CCS≤6 and or > 6 in the overall population (p < 0.0001****), in males (p = 0.0016**) and in females (p = 0.015*). b. Scatter plot representation of serum IL-6 levels in the control and FSHD1 patient. A significant difference in serum IL-6 levels was obtained between control and patients in the overall population (p = 0.006**), in males (p = 0.027*), and in females (p = 0.011*).

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  Fig. 4. FSHD-like mouse model: IL-6 levels in the serum and muscle. ACTA1-MCM/ + with TMX (control), ACTA1-MCM, FLExD/ + no TMX (mild) and ACTA1-MCM, FLExD/ + 7 days post-TMX (Severe D7) mice were assessed for muscle function and IL-6 levels. Ex vivo muscle physiology assessment of extensor digitorum longus muscle in each group of mice (a., b.): Control, blue (n = 9), Mild, green (n = 10), and Severe D7, red (n = 11). Mice were assessed for maximum tetanus (a.), and cross-sectional muscle area normalized specific tetanus (b.). IL-6 levels in the serum (c.) and gastrocnemius muscle (d.) in each group of mice: Control, blue (n = 6 in serum, n = 10 in muscle), Mild, green (n = 8 in serum, n = 10 in muscle), and Severe D7 (n = 6 in serum, n = 10 in muscle). Red dots in panels c and d depict corresponding samples used for serum and muscle analysis. Orange dots in panel d represent samples exclusively used for muscle analysis. Significance: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.