CXCL13 concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other neurological disorders determined by Luminex and ELISA

Markowicz, Mateusz; Schötta, Anna‐Margarita; Kundi, Michael; Bogovič, Petra; Ogrinc, Katarina; Strle, Franc; Stanek, Gerold

doi:10.1016/j.ttbdis.2018.04.008

Cited by 31 publications

(39 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This correlation seems to further support the view that CXCL13 concentrations in CSF can be useful when evaluating children with suspected LNB, in cases when antibody production is not yet present. Furthermore, applying a linearized cut-off for evaluation of CXCL13 (i.e., using an algorithm in which both the level of the CXCL13 and the pleocytosis in the specific patient is included), as suggested by Markowicz et al [ 31 ], could be an interesting way to further improve the diagnostic performance of CXCL13 in LNB.…”

Section: Discussionmentioning

confidence: 99%

The chemokine CXCL13 in cerebrospinal fluid in children with Lyme neuroborreliosis

Henningsson

Lager

Brännström

et al. 2018

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

Anti-Borrelia antibodies in the cerebrospinal fluid (CSF) are required for definite diagnosis of Lyme neuroborreliosis (LNB). However, children often present with early LNB, and antibody production in the CSF may not be demonstrated. Recent studies have suggested the chemokine CXCL13 to be an early marker for LNB. The aim of the study was to evaluate CXCL13 for laboratory diagnosis in pediatric LNB patients and to evaluate the association with pleocytosis in CSF, clinical features, and recovery. CSF samples were collected from LNB patients, classified as definite LNB (n = 44) or possible LNB (n = 22), and controls classified as non-LNB (n = 102) or other specific diagnoses (n = 23). CSF samples were analyzed with the recomBead CXCL13 assay (Mikrogen Diagnostik, Germany), cut-off 160 pg/mL. CXCL13 was significantly higher in LNB patients compared to controls (p < 0.001). Among LNB patients, 58/66 had elevated CXCL13, and among controls, 111/125 had CXCL13 levels under cut-off (sensitivity 88%, specificity 89%). In LNB patients with pleocytosis but no detectable anti-Borrelia antibodies in CSF (possible LNB), CXCL13 was elevated in 16/22 (73%). A weak correlation between CXCL13 and pleocytosis in CSF was found in LNB patients (Rho = 0.46, p < 0.01), but no differences in CXCL13 levels in relation to specific clinical features. In conclusion, CXCL13 is elevated in CSF in children with LNB, showing acceptable sensitivity and specificity. In patients with possible LNB, CXCL13 was elevated in a majority of cases (73%) and is suggested as a complementary diagnostic tool in pediatric LNB patients. CXCL13 was not associated with specific clinical features or recovery.

show abstract

Section: Discussionmentioning

confidence: 99%

The chemokine CXCL13 in cerebrospinal fluid in children with Lyme neuroborreliosis

Henningsson

Lager

Brännström

et al. 2018

Eur J Clin Microbiol Infect Dis

View full text Add to dashboard Cite

show abstract

“…CXCL13 also occurs in CNS inflammation and is the focus of biomarker research for Lyme neuroborreliosis (LNB), CNS lymphoma, and multiple sclerosis (MS) [8]. The broad spectrum of CNS inflammatory conditions with CXCL13 elevations in CSF also include bacterial/ viral and aseptic meningitis, encephalitis, myelitis, and autoimmune encephalitis [9][10][11][12][13][14]. The function of CSF CXCL13 is only partly established and mainly attributed to B cell chemoattraction to the CNS [15].…”

Section: Open Accessmentioning

confidence: 99%

Chemokine CXCL13 in serum, CSF and blood–CSF barrier function: evidence of compartment restriction

Pilz

Sakic

Wipfler

et al. 2020

Fluids Barriers CNS

View full text Add to dashboard Cite

Background and purpose: Elevation of the chemokine CXCL13 in CSF frequently occurs during active and acute CNS inflammatory processes and presumably is associated with B cell-related immune activation. Elevation levels, however, vary a lot and "leaking" of CXCL13 from blood across dysfunctional brain barriers is a possible source. The aim was to clarify the relation between CXCL13 concentrations in CSF, CXCL13 concentrations in serum and blood-CSF barrier (BCSFB) function for a correct interpretation of the intrathecal origin of CXCL13. Methods: We retrospectively analyzed CXCL13 of banked CSF/serum samples (n = 69) selected from patient records and categorized the CSF CXCL13 elevations as CXCL13 negative (< 30 pg/ml), low (30-100 pg/ml), medium (101-250 pg/ml), or high (> 250 pg/ml). CXCL13 concentrations in CSF and serum and the corresponding CSF/serum CXCL13 quotients (Qcxcl13) were compared to CSF/serum albumin quotients (QAlb) as a measure for BCSFB function. The CXCL13 negative category included two subgroups with normal and dysfunctional BCSFB. Results: Serum CXCL13 concentrations were similar across categories with median levels around 100 pg/ml but differed between individuals (29 to > 505 pg/ml). Despite clear evidence in serum, CXCL13 was detectable only at trace amounts (medians 3.5 and 7.5 pg/ml) in CSF of the two CXCL13 negative subgroups irrespective of a normal or pathological QAlb. Moreover, we found no association between CSF and serum CXCL13 levels or between QAlb and CSF CXCL13 levels in any of the CSF CXCL13-delineated categories. CXCL13 apparently does not "leak" from blood into CSF. This implies an intrathecal origin also for low CSF CXCL13 levels and a caveat for analyzing the Qcxcl13, because higher serum than CSF concentrations arithmetically depress the Qcxcl13 resulting in misleadingly low CSF/serum quotients. Conclusion: We demonstrated that CXCL13 does not cross from blood into CSF, not even during severe BCSFB dysfunction. CSF CXCL13 elevations therefore most likely always are CNS-derived, which highlights their relevance as indicator of inflammatory CNS processes. We recommend data should not be corrected for BCSFB permeability (QAlb) and not to calculate CSF/serum quotients for CXCL13 as these may introduce error.

show abstract

“…Nine full-text articles were assessed for eligibility. Four studies were finally retained: two meta-analyses [40,41], one retrospective controlled study [42] and one prospective uncontrolled study [43]. QUADAS-2 quality assessment demonstrated low risk of bias and low applicability concerns for both meta-analyses [40,41], unclear risk of bias and uncertainty regarding applicability for the retrospective controlled study [42], and high risk of bias and high concerns regarding applicability for the prospective uncontrolled study [43].…”

Section: Tests Exploring Inflammatory or Autoimmune Responses Cxcl-13mentioning

confidence: 99%

“…Optimal cut-off values were determined to be 162 pg/mL in one meta-analysis [41] and 131 pg/mL using the Luminex platform versus 259 pg/mL for ELISA in a retrospective, controlled study [42]. Cut-off determination is a major issue for CXCL-13 use to diagnose Lyme neuroborreliosis, because no official recommendation has yet been advanced.…”

Section: Tests Exploring Inflammatory or Autoimmune Responses Cxcl-13mentioning

confidence: 99%

“…Each laboratory has to determine its own threshold, which might lead to different interpretations. Moreover, the CSF CXCL-13 level is elevated in other central nervous system disorders, like neurosyphilis, cryptococcosis, trypanosomiasis, viral meningitides, meningoencephalitides and central nervous system lymphoma [41,42]. Attention should also be paid to those pathologies when interpreting the results.…”

Section: Tests Exploring Inflammatory or Autoimmune Responses Cxcl-13mentioning

confidence: 99%

See 1 more Smart Citation

Unconventional diagnostic tests for Lyme borreliosis: a systematic review

Raffetin

Saunier²,

Bouiller

et al. 2020

Clinical Microbiology and Infection

View full text Add to dashboard Cite

Background: Lyme borreliosis (LB) diagnosis currently relies mainly on serological tests and sometimes PCR or culture. However, other biological assays are being developed to try to improve Borrelia-infection diagnosis and/or monitoring. Objectives: To analyse available data on these unconventional LB diagnostic assays through a systematic literature review. Methods: We searched PubMed and Cochrane Library databases according to the PRISMA-DTA method and the Cochrane Handbook for Systematic Reviews of Interventions. We analysed controlled and uncontrolled studies (published 1983e2018) on biological tests for adults to diagnose LB according to the European Study Group for Lyme Borreliosis or the Infectious Diseases Society of America definitions, or identify strongly suspected LB. Two independent readers evaluated study eligibility and extracted data from relevant study reports; a third reader analysed full texts of papers to resolve disagreements. The quality of each included study was assessed with the QUADAS-2 evaluation scale. Results: Forty studies were included: two meta-analyses, 25 prospective controlled studies, five prospective uncontrolled studies, six retrospective controlled studies and two case reports. These biological tests assessed can be classified as: (i) proven to be effective at diagnosing LB and already in use (CXCL-13 for neuroborreliosis), but not enough to be standardized; (ii) not yet used routinely, requiring further clinical evaluation (CCL-19, OspA and interferon-a); (iii) uncertain LB diagnostic efficacy because of controversial results and/or poor methodological quality of studies evaluating them (lymphocyte transformation test, interferon-g, ELISPOT); (iv) unacceptably low sensitivity and/or specificity (CD57 þ natural killer cells and rapid diagnostic tests); and (v) possible only for research purposes (microscopy and xenodiagnoses). Discussion: QUADAS-2 quality assessment demonstrated high risk of bias in 25/40 studies and uncertainty regarding applicability for 32/40, showing that in addition to PCR and serology, several other LB diagnostic assays have been developed but their sensitivities and specificities are heterogeneous and/or under-evaluated or unassessed. More studies are warranted to evaluate their performance parameters.

show abstract

CXCL13 concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other neurological disorders determined by Luminex and ELISA

Cited by 31 publications

References 19 publications

The chemokine CXCL13 in cerebrospinal fluid in children with Lyme neuroborreliosis

The chemokine CXCL13 in cerebrospinal fluid in children with Lyme neuroborreliosis

Chemokine CXCL13 in serum, CSF and blood–CSF barrier function: evidence of compartment restriction

Unconventional diagnostic tests for Lyme borreliosis: a systematic review

Contact Info

Product

Resources

About