Abstract
BackgroundIt has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited.MethodsWe longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease.ResultsIn the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34–11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0–498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL.ConclusionsWe confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.
Highlights
It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections
The lack of detectable Borrelia burgdorferi (Bb)-specific antibody production can be seen in patients during the first few weeks of disease and, in a small number of patients, CSF pleocytosis may be absent for the first days of disease [17,18]
We show a significant correlation between CSF mononuclear cells and CXCL13 (Figure 4A), but the correlation is not perfect and elevated CSF CXCL13 levels are seen in HIV patients without mononuclear pleocytosis
Summary
It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. European guidelines require clinical symptoms consistent with LNB, such as painful meningoradiculitis, other diagnoses excluded, cerebrospinal fluid (CSF) pleocytosis and intrathecal Borrelia burgdorferi (Bb) antibody production [2,3]. Higher CSF CXCL13 concentrations are recorded in LNB than in several other infectious and inflammatory CNS diseases [6,7,8]. Cryptococcosis and neurosyphilis are among the few other infectious diseases in which CSF CXCL13 levels as high as those in LNB have been reported [9,10]
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