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Kynurenic acid may underlie sex-specific immune responses to COVID-19
Science Signaling ( IF 7.3 ) Pub Date : 2021-07-06 , DOI: 10.1126/scisignal.abf8483
Yuping Cai 1, 2 , Daniel J Kim 3 , Takehiro Takahashi 3 , David I Broadhurst 4 , Hong Yan 1 , Shuangge Ma 5 , Nicholas J W Rattray 6 , Arnau Casanovas-Massana 7 , Benjamin Israelow 3, 8 , Jon Klein 3 , Carolina Lucas 3 , Tianyang Mao 3 , Adam J Moore 7 , M Catherine Muenker 7 , Ji Eun Oh 3 , Julio Silva 3 , Patrick Wong 3 , , Albert I Ko 7 , Sajid A Khan 9 , Akiko Iwasaki 3, 10 , Caroline H Johnson 1
Affiliation  

Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males.



中文翻译:

犬尿酸可能是对 COVID-19 的性别特异性免疫反应的基础

2019 年冠状病毒病 (COVID-19) 在男性中的临床结果比女性差,而免疫反应是这些性别相关差异的基础。由于免疫反应在一定程度上受代谢物的调节,因此我们检查了 COVID-19 患者的血清代谢物。在男性患者中,犬尿酸 (KA) 和高 KA 与犬尿氨酸 (K) 比值 (KA:K) 与年龄、炎性细胞因子和趋化因子呈正相关,与 T 细胞反应呈负相关。临床恶化的男性的 KA:K 高于稳定的男性。KA 抑制谷氨酸释放,临床恶化并与免疫反应相关的患者谷氨酸丰度较低。基因型-组织表达 (GTEx) 项目的数据分析表明,编码产生 KA 的酶的基因的表达,犬尿氨酸氨基转移酶,与老年男性的细胞因子丰度和免疫反应激活相关。这项研究表明,KA 与 COVID-19 的免疫反应和临床结果具有性别特异性联系,这表明男性代谢物和免疫反应之间存在正反馈。

更新日期:2021-07-07
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