Accelerated kynurenine pathway downregulates immune activation in patients with axial spondyloarthritis

Yurt, Emine Feyza; Bıçer, Cemile; Serdar, Muhittin; Akan, Selcuk; Erten, Şükran

doi:10.1016/j.cyto.2023.156247

Cited by 2 publications

(18 citation statements)

References 36 publications

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“…After full-text revision of the remaining 28 articles, two were further excluded because of missing data, one because it was not a case-control study, and one because it was conducted in participants <18 years of age. 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 ).…”

Section: Resultsmentioning

confidence: 99%

“…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%

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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The kynurenine pathway in patients with rheumatoid arthritis during tumor necrosis factor α inhibitors treatment

Witoszyńska-Sobkowiak,

Sikorska,

Niklas

et al. 2024

Reumatologia

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ObjectivesThe importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis (RA). The aim of the study was to evaluate the effect of treatment with tumor necrosis factor α (TNF-α) inhibitors on the activity of the kynurenine pathway in patients with RA.Material and methodsThis was an investigator-initiated, prospective, observational study. The study was performed on 30 RA patients (Caucasian, 11 male, 19 female; mean age 45 ±16 years) treated with TNF-α inhibitors. All patients were assessed before and after 6 months of therapy. As a control group, age- and sex-matched, 20 healthy volunteers were recruited. Disease activity was evaluated by the Modified Disease Activity Score with 28-joint count (DAS28). Inflammatory markers were assessed routinely by the hospital central laboratory. Serum concentrations of kynurenine, serotonin and tryptophan were measured with specific immunoassays. To estimate indoleamine 2,3-dioxygenase (IDO) activity, kynurenine-to-tryptophan ratio was calculated.ResultsThe results of our study showed changes in tryptophan metabolism in RA patients, compared with healthy controls. Surprisingly, RA patients had statistically significant decreased kynurenine-to-tryptophan ratio (p = 0.003), which could indicate diminished IDO activation in RA. Moreover, we found no significant changes in kynurenine-to-tryptophan ratio after treated with TNF-α inhibitors (p = 0.490), despite disease remission. Additionally, tryptophan metabolism activity did not correlate with objective markers of inflammation.ConclusionsThe RA patients had altered tryptophan metabolism, compared with healthy controls. The mechanisms affecting tryptophan metabolism in RA may be complex. We believe that continuing elucidation of pathophysiological pathways relevant in RA offer substantial hope for the development of specific pharmacotherapy for treatment of RA – especially for comorbidity of RA and depression.

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Accelerated kynurenine pathway downregulates immune activation in patients with axial spondyloarthritis

Cited by 2 publications

References 36 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

The kynurenine pathway in patients with rheumatoid arthritis during tumor necrosis factor α inhibitors treatment

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