Cerebrospinal fluid cytokines in Lyme neuroborreliosis

Abstract

BackgroundLyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods. A few other cytokines have also been analyzed as possible diagnostic markers. However, multiplex analyses simultaneously evaluating the concentrations of a large number of different cytokines in the CSF of LNB patients have been lacking thus far. Extensive cytokine profiling CSF samples of LNB patients would also help in understanding the complex immunopathogenesis of LNB.MethodsCSF samples were analyzed from 43 LNB patients, 19 controls, 18 tick-borne encephalitis patients, and 31 multiple sclerosis patients. In addition, CSF samples from 23 LNB patients obtained after the antibiotic treatment were examined. Altogether, the concentrations of 49 different cytokines were determined from all of the samples. The concentrations of 48 different cytokines were analyzed by magnetic bead suspension array using the Bio-Plex Pro Human Cytokine 21- and 27-plex panels, and the concentration of CXCL13 was analyzed by an ELISA based method.ResultsDistinct cytokine profiles which were able to distinguish LNB patients from controls, tick-borne encephalitis patients, multiple sclerosis patients, and LNB patients treated with antibiotics were identified. LNB patients had elevated concentrations of all major T helper cell type cytokines (Th1, Th2, Th9, Th17, and Treg) in their CSF.ConclusionsDespite the great differences in the CSF cytokine profiles of different patient groups, CXCL13 still remained as the best marker for LNB. However, IL-1ra might also be helpful as a marker for the antibiotic treatment response. Concerning the immunopathogenesis, this is the first report suggesting the involvement of Th9 cells in the immune response of LNB.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0745-x) contains supplementary material, which is available to authorized users.

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

“…The finding of neutrophil activation in both LNB and EVM is intriguing, since these infections have similarities with respect to both clinical presentation and CSF cellular profile, which may include neutrophil predominance in the early phase [35]. Several studies have de facto shown the presence of neutrophil-activating cytokines and chemokines in the CSF samples of patients with LNB [36][37][38][39] and EVM [40,41], and the production of neutrophil chemo-attractants, such as CXCL1, CXCL8 and CXCL10 after in vitro stimulation of neuronal cells in response to B. burgdorferi spirochaetes [42]. Thus, there appears to be a prerequisite for neutrophil recruitment into the CNS in infections caused by B. burgdorferi and enterovirus.…”

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

“…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,…”

Borrelia burgdorferiInfection and Lyme Disease in North American Horses: A Consensus Statement

“…The immunopathology of Lyme disease in people is still being elucidated, but many human patients have increased markers of inflammation and there is a role for Th1, Th2, Th9, Th17, and T‐reg in the immunopathology of the disease …”