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Kynurenic acid underlies sex-specific immune responses to COVID-19
Yuping Cai; Daniel J Kim; Takehiro Takahashi; David I Broadhurst; Shuangge Ma; Nicholas J.W Rattray; Arnau Casanovas-Massana; Benjamin Israelow; Jon Klein; Carolina Lucas; Tianyang Mao; Adam J Moore; Catherine M Muenker; Julio Silva; Patrick Wong; - Yale IMPACT Research team; Albert J Ko; Sajid A Khan; Akiko Iwasaki; Caroline H Johnson.
Afiliación
  • Yuping Cai; Department of Environmental Health Sciences, Yale School of Public Health
  • Daniel J Kim; Department of Immunobiology, Yale University School of Medicine
  • Takehiro Takahashi; Department of Immunobiology, Yale University School of Medicine
  • David I Broadhurst; Centre for Integrative Metabolomics & Computational Biology, School of Science, Edith Cowan University, Joondalup, 6027, Australia
  • Shuangge Ma; Department of Biostatistics, Yale School of Public Health
  • Nicholas J.W Rattray; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK.
  • Arnau Casanovas-Massana; Department of Epidemiology of Microbial Diseases, Yale School of Public Health
  • Benjamin Israelow; Department of Immunobiology, Yale University School of Medicine;Department of Internal Medicine, Section of Infectious Diseases, Yale University School of Medic
  • Jon Klein; Department of Immunobiology, Yale University School of Medicine
  • Carolina Lucas; Department of Immunobiology, Yale University School of Medicine
  • Tianyang Mao; Department of Immunobiology, Yale University School of Medicine
  • Adam J Moore; Department of Epidemiology of Microbial Diseases, Yale School of Public Health
  • Catherine M Muenker; Department of Epidemiology of Microbial Diseases, Yale School of Public Health
  • Julio Silva; Department of Immunobiology, Yale University School of Medicine
  • Patrick Wong; Department of Immunobiology, Yale University School of Medicine
  • - Yale IMPACT Research team;
  • Albert J Ko; Yale University School of Public Health
  • Sajid A Khan; Department of Surgery, Division of Surgical Oncology, Yale University School of Medicine
  • Akiko Iwasaki; Yale University School of Medicine;Howard Hughes Medical Institute
  • Caroline H Johnson; Department of Environmental Health Sciences, Yale School of Public Health
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20189159
ABSTRACT
Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined whether the serum metabolome has sex-specificity for immune responses in COVID-19. In males with COVID-19, kynurenic acid (KA) and a high KA to kynurenine (K) ratio was positively correlated with age, inflammatory cytokines, and chemokines and was negatively correlated with T cell responses, revealing that KA production is linked to immune responses in males. Males that clinically deteriorated had a higher KAK ratio than those that stabilized. In females with COVID-19, this ratio positively correlated with T cell responses and did not correlate with age or clinical severity. KA is known to inhibit glutamate release, and we observed that serum glutamate is lower in patients that deteriorate from COVID-19 compared to those that stabilize, and correlates with immune responses. Analysis of Genotype-Tissue Expression (GTEx) data revealed that expression of kynurenine aminotransferase, which regulates KA production, correlates most strongly with cytokine levels and aryl hydrocarbon receptor activation in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes, in COVID-19 infection.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint