| Autor: |
Erik W Anderson, Ying Jin, Andrew Shih, Arnon Arazi, Sara Goodwin, Julien Roeser, Richard A Furie, Cynthia Aranow, Bruce Volpe, Betty Diamond, Meggan Mackay |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Lupus Science & Medicine. 9:e000808 |
| ISSN: |
2053-8790 |
| DOI: |
10.1136/lupus-2022-000808 |
| Popis: |
ObjectiveQuinolinic acid (QA), a kynurenine (KYN)/tryptophan (TRP) pathway metabolite, is an N-methyl-D-aspartate receptor agonist that can produce excitotoxic neuron damage. Type I and II interferons (IFNs) stimulate the KYN/TRP pathway, producing elevated QA/kynurenic acid (KA), a potential neurotoxic imbalance that may contribute to SLE-mediated cognitive dysfunction. We determined whether peripheral blood interferon-stimulated gene (ISG) expression associates with elevated serum KYN:TRP and QA:KA ratios in SLE.MethodsISG expression (whole-blood RNA sequencing) and serum metabolite ratios (high-performance liquid chromatography) were measured in 72 subjects with SLE and 73 healthy controls (HCs). ISG were identified from published gene sets and individual IFN scores were derived to analyse associations with metabolite ratios, clinical parameters and neuropsychological assessments. SLE analyses were grouped by level of ISG expression (‘IFN high’, ‘IFN low’ and ‘IFN similar to HC’) and level of monocyte-associated gene expression (using CIBERSORTx).ResultsSerum KYN:TRP and QA:KA ratios were higher in SLE than in HC (pConclusionsHigh ISG expression correlated with elevated KYN:TRP ratios in subjects with SLE, suggesting IFN-mediated KYN/TRP pathway activation, and with QA:KA ratios in a subset with high monocyte-associated gene expression, suggesting that KYN/TRP pathway activation may be particularly important in monocytes. These results need validation, which may aid in determining which patient subset may benefit from therapeutics directed at the IFN or KYN/TRP pathways to ameliorate a potentially neurotoxic QA/KA imbalance. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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