Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation

• DOI: 10.1186/s12974-022-02658-w
• Publication Date: 2022-12-08T14:24:01Z
• Authors: Tatiane Assone; Soraya Maria Menezes; Fernanda de Toled...; Victor Angelo Fol...; Gabriela da Silva...; Tim Dierckx; Marcos Braz; Jerusa Smid; Michel E. Haziot; Rosa M. N. Marcusso; Flávia E. Dahy; Evelien Vanderlinden; Sandra Claes; Dominique Schols; Roberta Bruhn; Edward L. Murphy; Augusto César Pen...; Dirk Daelemans; Jurgen Vercauteren; Jorge Casseb; Johan Van Weyenbergh
• Keywords: Mononuclear; Clinical Sciences; Immunology; Motor Disorders; 610; 03 medical and health sciences; Clinical Research; Leukocytes; Corticosteroids; Humans; RC346-429; Inflammation; Human T-lymphotropic virus 1; 0303 health sciences; Neurology & Neurosurgery; Interleukin-6; Inflammatory and immune system; Research; Interleukin-17; Neurosciences; Evaluation of treatments and therapeutic interventions; Bayes Theorem; TSP; HTLV-I Infections; HAM; 3. Good health; Good Health and Well Being; HTLV-1; 6.1 Pharmaceuticals; Neuroinflammatory Diseases; Leukocytes, Mononuclear; Cytokines; Female; Neurology. Diseases of the nervous system; HAM/TSP

Abstract Background HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis therapeutic response in HAM/TSP, examined their interaction with Patients methods recruited 110 People living HTLV-1 (PLHTLV-1, 67 asymptomatic individuals 43 patients) total 946 person-years follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) GlycA were quantified by Cytometric Bead Array 1 NMR, respectively. Cytokine signaling prednisolone validated independent cohort nCounter digital transcriptomics. used multivariable regression, machine learning algorithms Bayesian network biomarker identification. Results found that IL-6 was positively correlated both age ( r = 0.50, p < 0.001) 0.45, 0.00049) asymptomatics, revealing ‘inflammaging” signature absent HAM/TSP. women 0.0069), did differ between the sexes. IFN-γ 0.007) IL-17A 0.0001) increased untreated Multivariable logistic regression identified determinants status, resulting modest accuracy predicting status (64.1%), while learning-derived decision tree classified patients 90.7% accuracy. Pre-treatment TNF significantly predicted worsening (measured Osame Motor Disability Scale), load. In addition, poor post-treatment levels. Likewise, transcriptomic IFN score, previously proposed CASP5/CXCL10/FCGR1A/STAT1 ), efficiently blunted vitro treatment PBMC from PLHTLV-1 incident Conclusions An age-related increase IL-6/GlycA reveals inflammaging PLHTLV-1, absence neurological disease. pre-treatment predict to pulse therapy, paving way precision medicine approach