Elevated serum levels of kynurenine pathway metabolites in patients with Behçet disease

Onmaz, Duygu Eryavuz; Tezcan, Dilek; Abuşoğlu, Sedat; Sivrikaya, Abdullah; Kuzu, Menekse; Yerlikaya, Fatma Hümeyra; Yılmaz, Sema; Ünlü, Ali

doi:10.1007/s00726-022-03170-4

Cited by 6 publications

(33 citation statements)

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“…Thus, 24 studies were selected for analysis ( Table 1 ) ( 26 – 49 ). The risk of bias, presented in Supplementary Table 3 , was moderate in 14 studies ( 26 – 35 , 37 , 41 , 44 , 45 , 47 ), and low in the remaining 10 ( 34 , 36 , 38 – 40 , 42 , 43 , 46 , 48 , 49 ). The initial certainty of evidence was low for all studies (rating 2, ⊕⊕⊝⊝) given their cross-sectional design.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…We identified 21 studies (23 comparator groups) reporting tryptophan concentrations in a total of 1,526 RD patients (mean age 48 years, 24% males) and 1,404 healthy controls (mean age 43 years, 38% males; Table 1 ) ( 26 – 38 , 40 – 42 , 44 , 46 – 49 ). Ten were conducted in Europe ( 26 – 29 , 32 – 37 ), and 11 in Asia ( 30 , 31 , 38 , 40 – 42 , 44 , 46 – 49 ). Six study groups included patients with RA ( 28 , 31 , 34 , 36 , 38 , 41 ), five with pSS ( 29 , 33 , 44 , 46 , 47 ), four with SLE ( 27 , 30 , 32 , 35 ), three with AS ( 38 , 40 ), two with SSc ( 26 , 37 ), and one with BD ( 42 ), FMF ( 48 ), and axSpA ( 49 ), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Ten were conducted in Europe ( 26 – 29 , 32 – 37 ), and 11 in Asia ( 30 , 31 , 38 , 40 – 42 , 44 , 46 – 49 ). Six study groups included patients with RA ( 28 , 31 , 34 , 36 , 38 , 41 ), five with pSS ( 29 , 33 , 44 , 46 , 47 ), four with SLE ( 27 , 30 , 32 , 35 ), three with AS ( 38 , 40 ), two with SSc ( 26 , 37 ), and one with BD ( 42 ), FMF ( 48 ), and axSpA ( 49 ), respectively. Liquid chromatography was used in 21 study groups ( 27 – 38 , 40 – 42 , 44 , 46 , 48 , 49 ), a spectrofluorimetric assay in one ( 26 ), and an enzyme-linked immunosorbent assay (ELISA) in the remaining one ( 47 ).…”

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases

Mangoni,

Zinellu

2023

Front. Immunol.

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There is an increasing interest in the pathophysiological role of the kynurenine pathway of tryptophan metabolism in the regulation of immune function and inflammation. We sought to address the link between this pathway and the presence rheumatic diseases (RD) by conducting a systematic review and meta-analysis of studies reporting the plasma or serum concentrations of tryptophan, kynurenine, and other relevant metabolites in RD patients and healthy controls. We searched electronic databases for relevant articles published between inception and the 30th of June 2023. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system. In 24 studies selected for analysis, compared to controls, RD patients had significantly lower tryptophan (standard mean difference, SMD= -0.71, 95% CI -1.03 to -0.39, p<0.001; I2 = 93.6%, p<0.001; low certainty of evidence), and higher kynurenine (SMD=0.69, 95% CI 0.35 to 1.02, p<0.001; I2 = 93.2%, p<0.001; low certainty), kynurenine to tryptophan ratios (SMD=0.88, 95% CI 0.55 to 1.21, p<0.001; I2 = 92.9%, p<0.001; moderate certainty), 3-hydroxykynurenine (SMD=0.74, 95% CI 0.30 to 1.18, p=0.001; I2 = 87.7%, p<0.001; extremely low certainty), and quinolinic acid concentrations (SMD=0.71, 95% CI 0.31 to 1.11, p<0.001; I2 = 88.1%, p<0.001; extremely low certainty). By contrast, there were non-significant between-group differences in kynurenic acid, 3-hydroxyanthranilic acid, kynurenic acid to kynurenine ratio, or quinolinic acid to kynurenine acid ratio. In meta-regression, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio were not associated with age, publication year, sample size, RD duration, C-reactive protein, or use of anti-rheumatic drugs and corticosteroids. In subgroup analysis, the SMD of tryptophan, kynurenine, and kynurenine to tryptophan ratio was significant across different types of RD, barring rheumatoid arthritis. Therefore, we have observed significant alterations in tryptophan, kynurenine, 3-hydroxykynurenine, and quinolinic acid concentrations in RD patients. Further research is warranted to determine whether these biomarkers can be useful for diagnosis and management in this patient group. (PROSPERO registration number: CRD CRD42023443718).Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD CRD42023443718.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases

Mangoni,

Zinellu

2023

Front. Immunol.

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“…However, we did not obtain the KYNA and QUIN concentration profiles among all groups in this study. The possible physiological reasons for the serum levels of KYNA, KYN, and QUIN being below the detectable thresholds are as follows: KYN production derived from gut microbiota permeated through the blood–brain barrier and converted into neurotoxic metabolites such as 3-HK, QUIN, and KYNA, which induced further neuronal damage ( Eryavuz et al, 2022 ). QUIN is produced from activated macrophages or microglia in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Profile and potential role of novel metabolite biomarkers, especially indoleacrylic acid, in pathogenesis of neuromyelitis optica spectrum disorders

et al. 2023

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Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory and demyelinating disorder that can lead to serious disability and mortality. Humoral fluid biomarkers with specific, convenient, and efficient profiles that could characterize and monitor disease activity or severity are very useful. We aimed to develop a sensitive and high-throughput liquid chromatography–tandem mass spectrometry (LC-MS)/MS-based analytical method for novel biomarkers finding in NMOSD patients and verified its function tentatively.Methods: Serum samples were collected from 47 NMOSD patients, 18 patients with other neurological disorders (ONDs), and 35 healthy controls (HC). Cerebrospinal fluid (CSF) samples were collected from 18 NMOSD and 17 OND patients. Three aromatic amino acids (phenylalanine, tyrosine, and tryptophan) and nine important metabolites that included phenylacetylglutamine (PAGln), indoleacrylic acid (IA), 3-indole acetic acid (IAA), 5-hydroxyindoleacetic acid (HIAA), hippuric acid (HA), I-3-carboxylic acid (I-3-CA), kynurenine (KYN), kynurenic acid (KYNA), and quinine (QUIN) were analyzed by using the liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based method. The profile of IA was further analyzed, and its function was verified in an astrocyte injury model stimulated by NMO-IgG, which represents important events in NMOSD pathogenesis.Results: In the serum, tyrosine and some of the tryptophan metabolites IA and I-3-CA decreased, and HIAA increased significantly in NMOSD patients. The CSF levels of phenylalanine and tyrosine showed a significant increase exactly during the relapse stage, and IA in the CSF was also increased markedly during the relapse and remission phases. All conversion ratios had similar profiles with their level fluctuations. In addition, the serum IA levels negatively correlated with glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) levels in the serum of NMOSD patients were measured by using ultra-sensitive single-molecule arrays (Simoa). IA showed an anti-inflammatory effect in an in vitro astrocyte injury model.Conclusion: Our data suggest that essential aromatic amino acid tryptophan metabolites IA in the serum or CSF may serve as a novel promising biomarker to monitor and predict the activity and severity of NMOSD disease. Supplying or enhancing IA function can promote anti-inflammatory responses and may have therapeutic benefits.

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NAD+ as a Target for Cancer Treatment

Helman

Braidy

2023

Handbook of Cancer and Immunology

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Elevated serum levels of kynurenine pathway metabolites in patients with Behçet disease

Cited by 6 publications

References 50 publications

A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases

A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases

Profile and potential role of novel metabolite biomarkers, especially indoleacrylic acid, in pathogenesis of neuromyelitis optica spectrum disorders

NAD+ as a Target for Cancer Treatment

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