Impaired kynurenine metabolism in patients with primary Sjögren’s syndrome

Onmaz, Duygu Eryavuz; Tezcan, Dilek; Abuşoğlu, Sedat; Sak, Firdevs; Yerlikaya, Fatma Hümeyra; Yılmaz, Sema; Abuşoğlu, Gülsüm; Körez, Muslu Kazım; Ünlü, Ali

doi:10.1016/j.clinbiochem.2023.01.007

Cited by 4 publications

(40 citation statements)

References 40 publications

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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%

“…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 ). Among the liquid chromatography-based assays, seven used fluorimetric detection ( 27 – 33 ), and the remaining 14 mass spectrometry ( 34 – 38 , 40 – 42 , 44 , 46 , 48 , 49 ).…”

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%

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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Alteration in kynurenine pathway metabolites in young women with autoimmune thyroiditis

Krupa,

Łebkowska,

Kondraciuk

et al. 2024

Sci Rep

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The kynurenine pathway (KP) of tryptophan degradation includes several compounds that reveal immunomodulatory properties. The present study aimed to investigate the alteration in KP metabolites in young women with autoimmune thyroiditis (AIT) and their associations with thyroid function. The thyroid function tests, antithyroid antibodies measurement and ultrasonography of the thyroid gland have been performed in 57 young women with AIT and 38 age-matched healthy controls. The serum levels of tryptophan, kynurenine (KYN) and its metabolites were determined, and the activity of KP enzymes was calculated indirectly as product-to-substrate ratios. KP was activated and dysregulated in AIT, along with significantly elevated levels of KYN and anthranilic acid (AA), at the expense of the reduction of kynurenic acid (KYNA), which was reflected by the increase in the AA/KYNA ratio (p < 0.001). In univariate and multiple regression analyses, peripheral deiodinase (SPINA-GD) activity in AIT was positively associated with KYNA, AA, and quinolinic acid (QA). The merger of AA, AA/KYNA ratio, QA and SPINA-GD exhibited the highest sensitivity and specificity to predict AIT (p < 0.001) in receiver operating characteristic (ROC) analysis. In conclusion, the serum KYN metabolite profile is dysregulated in young women with AIT and could serve as a new predictor of AIT risk.

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The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects

Alves,

Moore,

Kell

2024

IJMS

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Kynurenic acid (KYNA) is an antioxidant degradation product of tryptophan that has been shown to have a variety of cytoprotective, neuroprotective and neuronal signalling properties. However, mammalian transporters and receptors display micromolar binding constants; these are consistent with its typically micromolar tissue concentrations but far above its serum/plasma concentration (normally tens of nanomolar), suggesting large gaps in our knowledge of its transport and mechanisms of action, in that the main influx transporters characterized to date are equilibrative, not concentrative. In addition, it is a substrate of a known anion efflux pump (ABCC4), whose in vivo activity is largely unknown. Exogeneous addition of L-tryptophan or L-kynurenine leads to the production of KYNA but also to that of many other co-metabolites (including some such as 3-hydroxy-L-kynurenine and quinolinic acid that may be toxic). With the exception of chestnut honey, KYNA exists at relatively low levels in natural foodstuffs. However, its bioavailability is reasonable, and as the terminal element of an irreversible reaction of most tryptophan degradation pathways, it might be added exogenously without disturbing upstream metabolism significantly. Many examples, which we review, show that it has valuable bioactivity. Given the above, we review its potential utility as a nutraceutical, finding it significantly worthy of further study and development.

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Impaired kynurenine metabolism in patients with primary Sjögren’s syndrome

Cited by 4 publications

References 40 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

Alteration in kynurenine pathway metabolites in young women with autoimmune thyroiditis

The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects

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