Borrelia burgdorferi specific serum and cerebrospinal fluid antibodies in Lyme neuroborreliosis

Publisher Copyright: © 2022 The Author(s)We used definite Lyme neuroborreliosis (LNB) adult patient acute and convalescent phase serum (n = 63 and 61, respectively) and cerebrospinal fluid (CSF; acute n = 63, 3 weeks timepoint n = 41) samples to characterize Borrelia burgdorferi specific antibody responses in patient subgroups categorized by demographics, infection manifestation and phase, infecting B. burgdorferi genospecies, received antibiotic treatments, and treatment outcome. B. burgdorferi antibodies were analyzed using 4 different assays incorporating a large array of antigens. We observed that B. burgdorferi specific serum antibodies show a universal, antigen independent declining trend after antibiotic treatment of LNB at 1 year. Antibodies declined similarly among women and men over time, and the decline was independent of patient age. The antibody responses were independent of the predominant LNB manifestation, treatment received by the patient, infecting B. burgdorferi genospecies, or the subjective improvement experienced by the patients. Finally, the antibody specificities in CSF reflected the specificities observed in serum samples.Peer reviewe

NMR metabolome of Borrelia burgdorferi in vitro and in vivo in mice

Lyme borreliosis (LB), caused by bacteria of the Borrelia burgdorferi sensu lato (Borrelia) species, isthe most common tick-borne infection in the northern hemisphere. LB diagnostics is based on clinicalevaluation of the patient and on laboratory testing, where the main method is the detection of Borreliaspecific antibodies in patient samples. There are, however, shortcomings in the current serology basedLB diagnostics, especially its inability to differentiate ongoing infection from a previously treated one.Identification of specific biomarkers of diseases is a growing application of metabolomics. One of themain methods of metabolomics is nuclear magnetic resonance (NMR) spectroscopy. In the presentstudy, our aim was to analyze whether Borrelia growth in vitro and infection in vivo in mice causesspecific metabolite differences, and whether NMR can be used to detect them. For this purpose,we performed NMR analyses of in vitro culture medium samples, and of serum and urine samples ofBorrelia infected and control mice. The results show, that there were significant differences in theconcentrations of several amino acids, energy metabolites and aromatic compounds between Borreliaculture and control media, and between infected and control mouse serum and urine samples. Forexample, the concentration of L-phenylalanine increases in the Borrelia growth medium and in serum ofinfected mice, whereas the concentrations of allantoin and trigonelline decrease in the urine of infectedmice. Therefore, we conclude that Borrelia infection causes measurable metabolome differences in vitroand in Borrelia infected mouse serum and urine samples, and that these can be detected with NMR.</p

Borrelia burgdorferi specific serum and cerebrospinal fluid antibodies in Lyme neuroborreliosis

We used definite Lyme neuroborreliosis (LNB) adult patient acute and convalescent phase serum (n = 63 and 61, respectively) and cerebrospinal fluid (CSF; acute n = 63,3 weeks timepoint n = 41) samples to characterize Borrelia burgdorferi specific antibody responses in patient subgroups categorized by demographics, infection manifestation and phase, infecting B. burgdorferi genospecies, received antibiotic treatments, and treatment outcome. B. burgdorferi antibodies were analyzed using 4 different assays incorporating a large array of antigens. We observed that B. burgdorferi specific serum antibodies show a universal, antigen independent declining trend after antibiotic treatment of LNB at 1 year. Antibodies declined similarly among women and men over time, and the decline was independent of patient age. The antibody responses were independent of the predominant LNB manifestation, treatment received by the patient, infecting B. burgdorferi genospecies, or the subjective improvement experienced by the patients. Finally, the antibody specificities in CSF reflected the specificities observed in serum samples.</p

Conserved lysine residues in decorin binding proteins of Borrelia garinii are critical in adhesion to human brain microvascular endothelial cells

Lyme borreliosis is a tick-borne disease caused by Borrelia burgdorferi sensu lato spirochetes (Lyme borreliae). When the disease affects the central nervous system, it is referred to as neuroborreliosis. In Europe, neuroborreliosis is most often caused by Borrelia garinii. Although it is known that in the host Lyme borreliae spread from the tick bite site to distant tissues via the blood vasculature, the adherence of Lyme borreliae to human brain microvascular endothelial cells has not been studied before. Decorin binding proteins are adhesins expressed on Lyme borreliae. They mediate the adhesion of Lyme borreliae to decorin and biglycan, and the lysine residues located in the binding site of decorin binding proteins are important to the binding activity. In this study, we show that lysine residues located in the canonical binding site can also be found in decorin binding proteins of Borrelia garinii, and that these lysines contribute to biglycan and decorin binding. Most importantly, we show that the lysine residues are crucial for the binding of Lyme borreliae to decorin and biglycan expressing human brain microvascular endothelial cells, which in turn suggests that they are involved in the pathogenesis of neuroborreliosis.</p