Diagnostic relevance of the chemokine CXCL13 and anti-C6 peptide antibodies in patients with neuroborreliosis
Abstract
Aim of the study: The study was focused on testing the diagnostic value of detection of the chemokine CXCL13 (B lymphocyte chemoattractant) and anti-C6 peptide (synthetic peptide derived from B. burdorferi VlsE protein) antibodies in patients with neuroborreliosis (NB). Material and methods: One hundred and twenty-nine patients with clinical suspicion of neuroinfection were included in the study.
Eighty patients with NB (positive for antibodies in serum and CSF) were subdivided into four groups (A1-A4) based on positivity/negativity of the antibody index (AI) and pleocytosis. The control group was composed of 49 patients with a negative AI and absence of CSF pleocytosis.
Chemokine CXCL13 and anti-C6 antibodies were examined by commercial kits (Human CXCL13/BLC/BCA-1 Immunoassay, R&D Systems, INC, USA and C6 B. burgdorferi (Lyme) ELISA, Immunetics Inc. USA).
The CXCL13 cut-off values were set to >= 130 pg/ml for the CSF and >= 62 pg/ml for the serum. Results: The highest CSF levels of CXCL13 chemokine were found in group A1 (pleocytosis, AI positive), and they were significantly higher (p < 0.001) comparing with other groups except A3 (pleocytosis, AI negative; p = 0.04).
Group A3 also showed significantly higher levels of CXCL13 than groups A2 (without pleocytosis, AI positive; p = 0.005), A4 (without pleocytosis, AI negative), and B (p < 0.001). The differences in the serum CXCL13 levels between groups were non-significant.
The serum anti-C6 antibodies were detected in all NB groups and the positivity rates did not differ between groups (92%) except for A3 where 55% of the patients were positive. In the CSF, the highest anti-C6 sensitivity was found in the patients with a positive AI (A1 88.6%; A2 76.9%) while in the groups with a negative AI, it was low (A3 25%; A4 0%).
In group B, anti-C6 antibodies were not detected. Conclusion: The highest CSF CXCL13 levels were found in early stage NB.
Elevated CXCL13 concentrations correlate better with pleocytosis than with AI positivity; however, there exist some patients with a positive AI who have low CXCL13 levels. These patients are most probably those in the late - subacute stage of neuroinfection.
The CXCL13 testing seems to be the most diagnostically helpful in the acute stage of NB where AI is still negative. The clinical sensitivity of the C6 ELISA test appears to be insufficient for CSF examination under our conditions.
On the contrary, the specificity of this test was proven high, because none of the controls tested positive.