Toll-like receptors and IL-7 as potential biomarkers for immune-mediated necrotizing myopathies

Abstract

We aimed to verify whether the immune system may represent a source of potential biomarkers for the stratification of immune-mediated necrotizing myopathies (IMNMs) subtypes. A group of 22 patients diagnosed with IMNM [7 with autoantibodies against signal recognition particle (SRP) and 15 against 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR)] and 12 controls were included. A significant preponderance of M1 macrophages was observed in both SRP⁺ and HMGCR⁺ muscle samples (p < 0.0001 in SRP⁺ and p = 0.0316 for HMGCR⁺ ), with higher values for SRP⁺ (p = 0.01). Despite the significant increase observed in the expression of TLR4 and all endosomal Toll-like receptors (TLRs) at protein level in IMNM muscle tissue, only TLR7 has been shown considerably upregulated compared to controls at transcript level (p = 0.0026), whereas TLR9 was even decreased (p = 0.0223). Within IMNM subgroups, TLR4 (p = 0.0116) mRNA was significantly increased in SRP⁺ compared to HMGCR⁺ patients. Within IMNM group, only IL-7 was differentially expressed between SRP⁺ and HMGCR⁺ patients, with higher values in SRP⁺ patients (p = 0.0468). Overall, innate immunity represents a key player in pathological mechanisms of IMNM. TLR4 and the inflammatory cytokine IL-7 represent potential immune biomarkers able to differentiate between SRP⁺ and HMGCR⁺ patients.

Keywords: Cytokines; Immune-mediated necrotizing myopathies (IMNMs); Innate immunity; Macrophages; Toll-like receptors.