Up-regulation of Borrelia-specific IL-4- and IFN-γ-secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis

Abstract

The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-gamma, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of 'confirmed NB' (n = 34), 'possible NB' (n = 30) and 'non-NB' (n = 10). The number of Borrelia-specific IL-4- and IFN-gamma-secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN-gamma was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN-gamma responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.

Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis

“…CXCL13, expressed as CSF-Serum CXCL13 ratio, reached a sensitivity of 99% and a specificity of 96% when studying group 1, definite LNB, and group 4, non-LNB, in line with previously published results (12)(13)20). Although negative in CSF ABA, 14 children of 16 patients in group 3b were interpreted as early LNB due to short symptom duration, typical symptoms, the presence of pleocytosis and serum antiborrelia antibodies, a classification which is also supported by the fact that a similarly defined group of children with possible LNB showed borrelia-specific T-cell responses to the same extent as children with definite LNB (21). Notably, all 14 children had a positive CSF-Serum CXCL13 ratio.…”

Seroprevalence of Borrelia IgG antibodies among young Swedish children in relation to reported tick bites, symptoms and previous treatment for Lyme borreliosis: a population-based survey

“…This finding cannot explain why some individuals have an antibody response when being exposed to the Borrelia spirochaete without developing symptoms of LB and why some individuals get clinical LB. However, children are known to have a Th2-skewed immunity and a different inflammatory response to LB compared to adults 21. Indeed, children with LB showed a stronger interleukin-4 response to Borrelia than adults with LB,21 suggesting that the quality of the cell-mediated response is of importance.…”

T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis

“…A number of peptides (OspA [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] [21,20]. Patients with treatment resistant Lyme arthritis have also been associated with the HLA-DR4, DR2 [27] and DRB1 [28,29], further supporting the involvement of an autoantigen in these patients.…”

“…In early experiments a few peptides were more able to stimulate lymphocytes from neuroborreliosis patients, namely no 1 (OspA [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Blood and CSF cells from patients and controls were stimulated with 29 different high-purity overlapping peptides from OspA ( Table 3). The peptides had a clearcut IFN-c stimulating capacity in lymphocytes from some patients, whereas cells from other patients hardly responded to any of the peptides.…”