Evaluating the Diagnostic Accuracy of Point-of-Care CXCL13 Measurements for Lyme Neuroborreliosis

Background: Measurements of the B-cell attracting chemokine CXCL13 in cerebrospinal fluid (CSF) has become increasingly popular in the diagnostic work-up for Lyme neuroborreliosis (LNB). ReaScan is a point-of-care test for CXCL13 with a short turnaround-time. However, the diagnostic cut-off value for LNB has not been firmly established. Methods: We conducted a retrospective cohort study including all ReaScan CXCL13 measurements performed on CSF samples at Copenhagen University Hospital, Rigshospitalet, from patients of all ages suspected for LNB in 2020–2025. Patients were categorized in accordance with the European Federation of Neurological Societies (EFNS) diagnostic guidelines for LNB as definite, possible, or non-LNB based on a retrospective review of patient records. The manufacturer-informed cut-off value for positive test results was applied and the diagnostic accuracy was calculated based on the ability to identify patients with possible and definite LNB. In addition, a Youden-index optimized cut-off value was calculated and evaluated on the cohort. Results: A total of 1181 ReaScan CXCL13 measurements from children and adults were evaluated against final diagnoses. Using the manufacturer-informed cut-off value (14 AU/mL) ReaScan CXCL13 reached a sensitivity of 38% and a specificity of 98% for identifying cases of possible and definite LNB. A Youden-index optimized cut-off value (1.79 AU/mL) significantly improved the diagnostic accuracy reaching a sensitivity value of 71% and a specificity of 92%. Conclusions: These real-world clinical data suggest that the current cut-off value for the ReaScan CXCL13 analysis is not optimal for diagnosing LNB. Lowering the cut-off level would significantly increase the diagnostic accuracy.