Retrospective Study Shows That Serum Levels of Chemokine CXCL10 and Cytokine GDF15 Support a Diagnosis of Sporadic Inclusion Body Myositis and Immune-Mediated Necrotizing Myopathy

回顾性研究表明趋化因子 CXCL10 和细胞因子 GDF15 的血清水平支持散发性包涵体肌炎和免疫介导的坏死性肌病的诊断

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作者:Boel De Paepe, Ken R Bracke, Jan L De Bleecker

Abstract

The implementation of novel blood-based biomarkers is desired to reduce the diagnostic delay and burden for myositis patients. In this retrospective study, the potential of C-X-C motif chemokine ligand 10 (CXCL10) and growth differentiation factor 15 (GDF15) was explored in an established patient cohort diagnosed with immune-mediated necrotizing myopathy (IMNM; n = 21), sporadic inclusion body myositis (IBM; n = 18), overlap myositis (OM; n = 3), dermatomyositis (DM; n = 2), and anti-synthetase syndrome (ASS; n = 1), comparing these results with healthy controls (n = 10) and patients with a hereditary neuromuscular disorder (n = 14). CXCL10 and GDF15 were quantified in sera with enzyme-linked immunosorbent assays and immunolocalized in skeletal muscle tissue. In myositis patients, serum CXCL10 levels were significantly increased 9.6-fold compared to healthy controls and 4.2-fold compared to disease controls. Mean levels of CXCL10 were 929 ± 658 pg/mL of serum in IBM and 425 ± 324 pg/mL of serum in IMNM. With the threshold set to 180 pg/mL of CXCL10, myositis patients could be differentiated from healthy and disease controls with a sensitivity of 0.80 and a specificity of 0.71. Incorporating a threshold of 300 pg/mL for GDF15 reduced false negatives to two IMNM patients only. Subsets of muscle-infiltrating immune cells expressed CXCL10, and serum levels correlated with muscle inflammation grade. We propose adding circulating CXCL10 and GDF15 to the blood-based diagnostic toolkit for myositis as a valuable patient-friendly approach.

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