Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chemokine CXCL10 and Cytokine GDF15 Associate with Autoimmune Myositis and Serum Levels Support Diagnosis and Subtyping

Version 1 : Received: 4 September 2023 / Approved: 6 September 2023 / Online: 7 September 2023 (13:35:58 CEST)

A peer-reviewed article of this Preprint also exists.

De Paepe, B.; Bracke, K.R.; De Bleecker, J.L. 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. Brain Sci. 2023, 13, 1369. De Paepe, B.; Bracke, K.R.; De Bleecker, J.L. 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. Brain Sci. 2023, 13, 1369.

Abstract

Implementation of novel blood-based biomarkers is desired to reduce 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), polymyositis (PM; n=3), dermatomyositis (DM; n=2), and anti-synthetase syndrome (ASS; n=1), comparing 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 and 4.2-fold compared to disease controls. Mean levels in IBM (929±658 pg/ml) were significantly higher than in IMNM (425±324 pg/ml). With the threshold set to 180pg/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.

Keywords

biomarker; C-X-C motif chemokine ligand 10; growth differentiation factor 15; idiopathic inflammatory myopathy; immune-mediated necrotizing myopathy; myositis; sporadic inclusion body myositis

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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