Abstract
IntroductionInfectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.MethodsThis was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.ResultsIn total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.ConclusionWe found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.
Highlights
Infectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy
In this prospective observational cohort study, we aimed to examine the induced immune response using the standardized functional immune assay TruCulture® in patients with infectious spondylodiscitis during and after antibiotic therapy
We found an increase in most of the induced immune responses as the patients were treated for infectious spondylodiscitis, and the overall cytokine release was within the reference range post-infection
Summary
Infectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Infectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that can disseminate to multiple foci, including the central nervous system. Disseminated spondylodiscitis is often complicated, and according to Danish Society of Infectious Diseases guidelines, the recommended duration of antibiotic therapy is six weeks in non-complicated and 12 weeks in complicated cases, respectively [2]. Despite extensive investigations with blood cultures and/or surgical biopsies, 10-30% of cases remain culture negative [3, 9] This underlines the relevance of early pathogen detection for optimal treatment, and different immune responses to these pathogens may be of clinical relevance
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