Abstract

Acute infectious spondylodiscitis (AIS) is a serious infection of the spine with rising incidence and a mortality of 3–6%. The role of the immune system in AIS is largely unknown. We performed extensive B and T-lymphocyte phenotyping in patients with AIS at diagnosis and after treatment cessation. In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and 3 months after treatment cessation. We additionally analysed levels of immunoglobulins and IgG subclasses, serum level and genetic variants of mannose-binding lectin, and somatic hypermutation. A total of 22 (61%) patients had B-lymphocytes below reference limit at baseline, persisting in 7 (30%) patients at follow-up. We found a lower proportion of CD19 + CD27 + IgD+ marginal zone B-lymphocytes and a higher proportion of γδ+ T-lymphocyte receptors compared with controls at both time points. Immunoglobulin levels were elevated at baseline compared to follow-up, and not associated with absolute B-lymphocyte count. In conclusion, a large proportion of AIS patients presented with profound B-lymphocyte deficiency, only partly reversible at follow-up. Identification of immune dysfunction related to AIS may allow for future targeted therapeutic interventions to restore host immunity.

Highlights

  • Acute infectious spondylodiscitis (AIS) is a serious infection of the spine, often requiring long term hospitalization

  • Four patients were treated for infection with mycobacteria, two of those culture positive for Mycobacterium tuberculosis (TB), one positive for atypical mycobacteria, one with culture-negative AIS treated according to clinical presentation of TB

  • There are no prior studies of the immune system in patients with AIS or osteomyelitis, there are casuistic reports of rare cases leading to evaluation of immunologic status[11,12,13] and in chronic osteomyelitis, studies have dealt with the interaction between immunological cells, bone resorption and treatment effect[14,15,16,17,18]

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Summary

Introduction

Acute infectious spondylodiscitis (AIS) is a serious infection of the spine, often requiring long term hospitalization. The reported mortality is between 3 to 6%, and up to half of patients undergo surgical intervention ranging from biopsy to stabilization of the spine[1,2,3,4,5]. The incidence of AIS varies between 4–24 cases/million/year and has been reported to be increasing as a consequence of an aging population and improved diagnostic procedures, primarily magnetic resonance imaging (MRI)[6,7,8,9]. The role of the immune system in acute infectious spondylodiscitis (AIS) is largely unknown, and, to our knowledge, there are no prior studies of the immune system in patients with AIS or osteomyelitis. That patients with primary AIS share common features of impaired immune function, and with this prospective multicenter study aimed to investigate major B and T-lymphocyte subpopulations, immunoglobulins, serum level and genetic variants of mannose-binding lectin and somatic hypermutation in patients with AIS at diagnosis and after treatment cessation

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