Kynurenine pathway of tryptophan metabolism in patients with familial Mediterranean fever

Abstract

Background Familial Mediterranean fever (FMF) is an autoinflammatory syndrome characterized by recurrent episodes of fever and aseptic polyserositis. Subclinical inflammation generates a hidden threat to the development of FMF complications such as amyloidosis in attack-free intervals. The kynurenine pathway (KP) has been considered an important player in inflammation and immune response. The study was aimed to measure serum levels of KP metabolites in patients with FMF in the attack-free period. Methods A total of 161 participants were recruited from the rheumatology department in this single-center, case-control study. Participants meeting the eligibility criteria were divided into healthy controls (n=80) and FMF (n=81). The laboratory data were obtained from the electronic registration database. Serum tryptophan, kynurenine, kynurenic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, quinolinic acid concentrations were measured with tandem mass spectrometry. Laboratory findings of FMF patients and healthy controls subjects were compared and evaluated. Results Serum tryptophan, kynurenic acid levels were significantly decreased in both FMF groups compared to the control group, while the levels of kynurenine, quinolinic acid, 3-hydroxykynurenine, the Kynurenine/Tryptophan ratio, and RDW were higher. Conclusion Tryptophan degradation by the KP is increased in patients with FMF. KP metabolites can be useful in demonstrating subclinical inflammation.

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

“…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.…”

“…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 ).…”

“…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 ).…”

“…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 ). Measurements were conducted in serum in 17 study groups ( 26 – 33 , 36 , 38 , 40 , 42 , 46 – 48 ), and plasma in the remaining six ( 34 , 35 , 37 , 41 , 44 , 49 ).…”

Recent Advances in Current Uptake Situation, Metabolic and Nutritional Characteristics, Health, and Safety of Dietary Tryptophan

“…6 The results showed that cerebrospinal fluid Trp levels were associated with 60-day mortality in tuberculous meningitis, and HIV-positive patients with high baseline cerebrospinal fluid Trp values or high systemic (plasma) KYN levels were at increased risk of death. Another investigation of familial Mediterranean fever (FMF) was initiated, 102 and the levels of Trp, KYN, KA, QA, and 3-HK in the serum were determined by mass spectrometry, and the results showed that in the FMF group, serum Trp, and KA levels were significantly lower, while KYN, QA, 3-HK levels, KYN/Trp ratio, and erythrocyte distribution width were higher, indicating the increased degradation of Trp by KP in FMF patients, and KP metabolites are useful in subclinical inflammation.…”