The potential for CXCL13 in CSF as a differential diagnostic tool in central nervous system infection

ABSTRACT

Introduction: Central nervous system (CNS) infections can be life-threatening and are often associated with disabling sequelae. One important factor in most CNS infections is a timely pathogen-specific treatment. The diagnostic methods available, however, do not always reach a satisfying sensitivity and specificity. In these cases, there is need for additional diagnostic biomarkers. Chemokines represent potential candidates as biomarkers, since they are an important pillar of the host immune response. The aim of this review is to discuss the diagnostic potential of cerebrospinal fluid (CSF) CXCL13 in patients with CNS infections.

Areas covered: Data were obtained from a literature search in PubMed up to October 2019. This review focusses on articles on the potential of CXCL13 as a diagnostic tool. The majority of identified studies aimed to characterize its role in two diseases, namely Lyme neuroborreliosis and neurosyphilis.

Expert opinion: CSF CXCL13 has a significant potential as a diagnostic and monitoring add-on marker in Lyme neuroborreliosis. Differences in study design, control groups and clinical parameters between studies, however, affect sensitivity, specificity and cutoff values, underlining the need of further studies to address these issues and pave the way for a generalized clinical practice.

KEYWORDS:

• Biomarker
• central nervous system infection
• cerebrospinal fluid
• CXCL13
• neuroborreliosis
• neurosyphilis

Article highlights

• CNS infections are potentially life-threatening and require a timely specific treatment. Early diagnosis can be difficult to make. In these cases, there is need for biomarkers that support a clinical diagnosis.

• CXCL13, together with its receptor CXCR5, plays an important role in B cell homeostasis and recruitment to the site of inflammation and/or infection.

• CXCL13 levels are elevated in the CSF of patients with Lyme neuroborreliosis and neurosyphilis

• CSF CXCL13 is a potentially helpful tool for diagnosis and monitoring the therapeutic response in neuroborreliosis.

• Among other disorders in which elevated CSF CXCL13 have been reported are CNS infections like trypanosomiasis and tick-borne encephalitis, but also non-infectious diseases like CNS lymphoma and neuroinflammatory diseases such as multiple sclerosis.

• Further prospective studies are needed to verify the diagnostic potential of CXCL13, e.g. in patients with suspected neuroborreliosis and negative borrelia-antibody-index or with early neurosyphilis and negative microbiological tests in the CSF.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.