TY - JOUR
T1 - Stimulated Immune Response by TruCulture® Whole Blood Assay in Patients With European Lyme Neuroborreliosis
T2 - A Prospective Cohort Study
AU - Ørbæk, Mathilde
AU - Gynthersen, Rosa Maja Møhring
AU - Mens, Helene
AU - Stenør, Christian
AU - Wiese, Lothar
AU - Brandt, Christian
AU - Ostrowski, Sisse Rye
AU - Nielsen, Susanne Dam
AU - Lebech, Anne Mette
N1 - Publisher Copyright:
© Copyright © 2021 Ørbæk, Gynthersen, Mens, Stenør, Wiese, Brandt, Ostrowski, Nielsen and Lebech.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/10
Y1 - 2021/5/10
N2 - Introduction: Borrelia burgdorferi sensu lato complex (B. burgdorferi) can cause a variety of clinical manifestations including Lyme neuroborreliosis. Following the tick-borne transmission, B. burgdorferi initially evade immune responses, later symptomatic infection is associated with occurrence of specific antibody responses. We hypothesized that B. burgdorferi induce immune hyporesponsiveness or immune suppression and aimed to investigate patients with Lyme neuroborreliosis ability to respond to immune stimulation. Methods: An observational cohort study investigating the stimulated immune response by standardized whole blood assay (TruCulture®) in adult patients with Lyme neuroborreliosis included at time of diagnosis from 01.09.2018-31.07.2020. Reference intervals were based on a 5-95% range of cytokine concentrations from healthy individuals (n = 32). Patients with Lyme neuroborreliosis and references were compared using Mann-Whitney U test. Heatmaps of cytokine responses were generated using the webtool Clustvis. Results: In total, 22 patients with Lyme neuroborreliosis (19 definite, 3 probable) were included. In the unstimulated samples, the concentrations of cytokines in patients with Lyme neuroborreliosis were comparable with references, except interferon (IFN)-α, interleukin (IL)-17A, IL-1β and IL-8, which were all significantly below the references. Patients with Lyme neuroborreliosis had similar concentrations of most cytokines in all stimulations compared with references. IFN-α, IFN-γ, IL-12 and IL-17A were lower than references in multiple stimulations. Conclusion: In this exploratory cohort study, we found lower or similar concentrations of circulating cytokines in blood from patients with Lyme neuroborreliosis at time of diagnosis compared with references. The stimulated cytokine release in blood from patients with Lyme neuroborreliosis was in general slightly lower than in the references. Specific patterns of low IL-12 and IFN-γ indicated low Th1-response and low concentrations of IL-17A did not support a strong Th17 response. Our results suggest that patients with Lyme neuroborreliosis elicit a slightly suppressed or impaired immune response for the investigated stimulations, however, whether the response normalizes remains unanswered.
AB - Introduction: Borrelia burgdorferi sensu lato complex (B. burgdorferi) can cause a variety of clinical manifestations including Lyme neuroborreliosis. Following the tick-borne transmission, B. burgdorferi initially evade immune responses, later symptomatic infection is associated with occurrence of specific antibody responses. We hypothesized that B. burgdorferi induce immune hyporesponsiveness or immune suppression and aimed to investigate patients with Lyme neuroborreliosis ability to respond to immune stimulation. Methods: An observational cohort study investigating the stimulated immune response by standardized whole blood assay (TruCulture®) in adult patients with Lyme neuroborreliosis included at time of diagnosis from 01.09.2018-31.07.2020. Reference intervals were based on a 5-95% range of cytokine concentrations from healthy individuals (n = 32). Patients with Lyme neuroborreliosis and references were compared using Mann-Whitney U test. Heatmaps of cytokine responses were generated using the webtool Clustvis. Results: In total, 22 patients with Lyme neuroborreliosis (19 definite, 3 probable) were included. In the unstimulated samples, the concentrations of cytokines in patients with Lyme neuroborreliosis were comparable with references, except interferon (IFN)-α, interleukin (IL)-17A, IL-1β and IL-8, which were all significantly below the references. Patients with Lyme neuroborreliosis had similar concentrations of most cytokines in all stimulations compared with references. IFN-α, IFN-γ, IL-12 and IL-17A were lower than references in multiple stimulations. Conclusion: In this exploratory cohort study, we found lower or similar concentrations of circulating cytokines in blood from patients with Lyme neuroborreliosis at time of diagnosis compared with references. The stimulated cytokine release in blood from patients with Lyme neuroborreliosis was in general slightly lower than in the references. Specific patterns of low IL-12 and IFN-γ indicated low Th1-response and low concentrations of IL-17A did not support a strong Th17 response. Our results suggest that patients with Lyme neuroborreliosis elicit a slightly suppressed or impaired immune response for the investigated stimulations, however, whether the response normalizes remains unanswered.
KW - Borrelia burgdorferi sensu lato complex
KW - innate immune system
KW - Lyme neuroborreliosis
KW - stimulated immune response
KW - TruCulture
KW - whole blood assay
KW - Prospective Studies
KW - Humans
KW - Interleukin-12
KW - Immunity
KW - Adult
KW - Lyme Disease
KW - Cohort Studies
KW - Lyme Neuroborreliosis
UR - http://www.scopus.com/inward/record.url?scp=85106895329&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2021.666037
DO - 10.3389/fcimb.2021.666037
M3 - Journal article
C2 - 34041044
AN - SCOPUS:85106895329
SN - 2235-2988
VL - 11
JO - Frontiers in cellular and infection microbiology
JF - Frontiers in cellular and infection microbiology
M1 - 666037
ER -