The Kynurenine Pathway is Differentially Activated in Children with Lyme Disease and Tick-Borne Encephalitis

Wickström, Ronny; Fowler, Åsa; Goiny, Michel; Millischer, Vincent; Ygberg, Sofia; Schwieler, Lilly

doi:10.3390/microorganisms9020322

Cited by 7 publications

(5 citation statements)

References 54 publications

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“…Previous research demonstrated alterations in kynurenine pathway activity following infection (23-25). Therefore, we investigated alterations in kynurenine pathway metabolite levels.…”

Section: Resultsmentioning

confidence: 98%

Increased levels of circulating neurotoxic metabolites in patients with mild Covid19

Santiago-Mujika

Heinrich

George

et al. 2022

Preprint

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SARS-CoV-2 corona virus causes a multi-faceted and poorly defined clinical and pathological phenotype involving hyperinflammation, cytokine release. And long-term cognitive deficits, with an undefined neuropathological mechanism. Inflammation increases the activity of the kynurenine pathway, which is linked to neurodegenerative and psychiatric disorders. We sought to determine whether the kynurenine pathway is impacted in patients with mild COVID-19, leading to elevated neurotoxic metabolites in blood, and whether such changes are associated with pro-inflammatory cytokines. Serum samples were taken from 150 patients and analyzed by ELISA and ultra-high performance liquid chromatography (UHPLC). The data were analyzed using multiple linear regression models adjusted for age and sex. We found increased levels of kynurenine, quinolinic acid and 3-hydroxykynurenine in serum from patients with mild COVID-19, together with increased levels of IL-6, ICAM-1, VCAM-1 and neopterin. The levels of neurotoxic metabolites were significantly associated with key inflammatory cytokines including IL-6 and TNFα. The COVID-19 risk-factor hypertension was associated with the highest levels of neurotoxic metabolites in plasma. These neuroactive metabolites could be part of the pathological mechanisms underlying cognitive impairment during and post-COVID and should be explored as potential biomarkers for long-COVID symptoms.

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“…Previous research demonstrated alterations in kynurenine pathway activity following infection (23-25). Therefore, we investigated alterations in kynurenine pathway metabolite levels.…”

Section: Resultsmentioning

confidence: 98%

Increased levels of circulating neurotoxic metabolites in patients with mild Covid19

Santiago-Mujika

Heinrich

George

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Overall, our current findings concerning the levels of kynurenines in CSF among healthy individuals are in agreement with previous studies and starkly differs from those seen in patients with infectious diseases where these levels are notably heightened. 60 - 62 This incongruity highlights the profound influence of the immune system in modulating the activity of the kynurenine pathway. One significant discovery is the inability to predict brain KYNA levels based solely on plasma analysis.…”

Section: Discussionmentioning

confidence: 99%

Kynurenine Metabolites in CSF and Plasma in Healthy Males

Orhan,

Schwieler,

Engberg

et al. 2024

Int J�Tryptophan�Res

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In recent years, kynurenine metabolites generated by tryptophan catabolism have gained increasing attention in the context of brain diseases. The question of importance is whether there is a relationship between peripheral and central levels of these metabolites. Some of these compounds do not cross the blood-brain barrier; in particular, kynurenic acid, and most analyses of kynurenines from psychiatric patients have been performed using plasma samples. In the present study, we recruited 30 healthy volunteers with no history of psychiatric or neurological diagnosis, to analyze tryptophan, kynurenine, kynurenic acid, and quinolinic acid levels in CSF and plasma. In addition, kynurenic acid was analyzed in urine. The most important finding of this study is that CSF kynurenic acid levels do not correlate with those in plasma or urine. However, we found a correlation between plasma kynurenine and CSF kynurenic acid. Further, plasma kynurenine and plasma quinolinic acid were correlated. Our findings clarify the distribution of tryptophan and its metabolites in various body compartments and may serve as a guide for the analysis of these metabolites in humans. The most significant finding of the present study is that a prediction of brain kynurenic acid by of the analysis of the compound in plasma cannot be made.

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“…Generally, the clinical outcome is significantly better in children compared to adults, and long-term neuropsychological disorders are not commonly seen in the pediatric population. In contrast, adults may experience cognitive disorders and persistent or recurrent neurological symptoms [55,56]. Additionally, regarding diagnostic testing, the sensitivity of the test using the VlsE/C6 antigen for neuroborreliosis in children may vary.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Precision in Lyme borreliosis: Assessing VlsE and C6 Antigens in a Pediatric Cohort

Wozinska,

Toczylowski,

Lewandowski

et al. 2023

Diagnostics

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(1) Background: Lyme borreliosis (LB) is a tick-borne disease known for its diagnostic challenges. Conventional two-tiered testing (CTTT) for antibodies is time-consuming, has low sensitivity in the early stages of disease, and sometimes generates false-positive IgM immunoblots. To tackle this issue, modified two-tiered testing (MTTT) was introduced, incorporating recombinant VlsE and C6 antigens to enhance diagnostic accuracy. (2) Methods: In this prospective study, we enrolled children exhibiting symptoms indicative of LB. We collected serum samples at various intervals and subjected them to analysis using standard enzyme immunoassays. We then compared these results with the outcomes from the VlsE and C6 assays. (3) Results: In our study, all 33 patients displaying erythema migrans (EM), a characteristic symptom of LB, exhibited positive responses to the C6 antigen. This finding underscores the potential utility of the C6 antigen as a reliable diagnostic tool for LB. Additionally, we observed a significant reduction in anti-VlsE antibody levels following antibiotic treatment in EM patients. (4) Conclusions: The utilization of recombinant VlsE and C6 antigens in LB diagnostics and monitoring has yielded promising results. Nonetheless, it is imperative for clinicians to exercise caution and interpret results in conjunction with clinical findings, considering the dynamic nature of medical guidelines. Even with recombinant antigen tests, some children with EM tested negative, highlighting the importance of clinical diagnosis for treatment decisions. Furthermore, clinicians should be mindful of the possibility of persistently positive VlsE/C6 test results during LB treatment monitoring.

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The Kynurenine Pathway is Differentially Activated in Children with Lyme Disease and Tick-Borne Encephalitis

Cited by 7 publications

References 54 publications

Increased levels of circulating neurotoxic metabolites in patients with mild Covid19

Increased levels of circulating neurotoxic metabolites in patients with mild Covid19

Kynurenine Metabolites in CSF and Plasma in Healthy Males

Diagnostic Precision in Lyme borreliosis: Assessing VlsE and C6 Antigens in a Pediatric Cohort

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