The recomBead Borrelia antibody index, CXCL13 and total IgM index for laboratory diagnosis of Lyme neuroborreliosis in children

Abstract

For laboratory diagnostics of Lyme neuroborreliosis (LNB), the recomBead Borrelia antibody index (AI) assay has shown promising results in a mixed age population, but has not previously been evaluated with specific focus on paediatric patients. The aim of the study was to evaluate the recomBead Borrelia AI assay in cerebrospinal fluid (CSF) for the laboratory diagnosis of LNB in children. We also wanted to explore whether early markers, such as CXCL13 in CSF and/or total IgM index could be useful as complementary diagnostic tools. Children being evaluated for LNB in a Swedish Lyme endemic area were included in the study (n = 146). Serum and CSF were collected on admission. Patients with other specific diagnoses were controls (n = 15). The recomBead Borrelia AI assay and the recomBead CXCL13 assay (Mikrogen) were applied together with total IgM index. The overall sensitivity for recomBead Borrelia AI (IgM and IgG together) was 74% and the specificity was 97%. However, the highest sensitivity (91%) at an acceptable level of specificity (90%) was obtained by recomBead Borrelia AI together with CXCL13 and total IgM index, showing a positive predictive value of 84% and a negative predictive value of 95%. Thus, the recomBead Borrelia AI assay performs with moderate sensitivity and high specificity in paediatric LNB patients. The major advantage seems to be increased sensitivity in the possible LNB group compared to the IDEIA assay. The diagnostic sensitivity may be further increased by using a combination of early markers, such as CXCL13 in CSF and total IgM index.

Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance

“…However, most studies measuring CXCL13 using ELISA and lateral flow (LFA) methods have shown elevated CXCL13 circulation levels in the CSF of patients with acute neuroborreliosis compared to other tested groups. Results of the available studies suggest its very high diagnostic value and report its high sensitivity and specificity [5][6][7][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. These studies are in agreement with a meta-analysis performed by Yang J. et al, who confirmed that CXCL13 has a high sensitivity and specificity for diagnosing neuroborreliosis [68].…”

“…The aims of pediatric studies included a reduction in mortality rates and control of the spread of infectious diseases. These studies have proven that CXCL13 concentration in the CSF of pediatric patients is significantly increased in neuroborreliosis compared to non-neuroborreliosis individuals [8,9,44,47]. One study revealed that differences in CXCL13 levels between children with neuroborreliosis and those with other conditions were statistically significant, although relatively small [45].…”

“…Neuroborreliosis CSF CXCL13 levels are highly elevated in NB compared to healthy and other non-inflammatory CNS diseases [5][6][7][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] CSF CXCL13 levels are significantly elevated in NB in comparison to NS [9,10,12] CSF CXCL13 concentrations are elevated in acute and possible NB with positive specific antibodies against Borrelia burgdorferi [5,34,[37][38][39][40] CSF CXCL13 concentrations correlate with WBC count and disease activity [41,42] CSF CXCL13 concentrations correlate better with pleocytosis than with CSF-specific antibodies [5,34,[37][38][39][40] CSF CXCL13 levels are highly elevated in NB patients with shorter disease duration [41,42] CSF CXCL13 levels are markedly elevated before treatment compared to after treatment [7,28,32,…”

“…For a positive combined test result, children needed to have a positive recomBead Borrelia antibody test and a positive CXCL13 or IgM index. Interestingly, in the neuroborreliosis group, 100% of the studied patients tested positive when a combination of tests was used [44]. Another study evaluated, in parallel, a combination of CSF-serum CXCL13 ratio and CSF-C6 antibodies.…”

A Neurologist's View of Lyme Disease and Other Tick-Borne Infections

“…Elevated in many inflammatory states, it appears to be disproportionately elevated in patients with LNB. 34,35 As such, it has been proposed as an adjunctive diagnostic marker. Although its specificity remains to be determined, 36 it does appear to decrease rapidly with effective treatment, making it a potential marker of treatment efficacy.…”