Premium
Indoleamine 2,3‐dioxygenase ( IDO )‐1 and IDO ‐2 activity and severe course of COVID ‐19
Author(s) -
Guo Lihui,
Schurink Bernadette,
Roos Eva,
Nossent Esther J,
Duitman Jan Willem,
Vlaar Alexander PJ,
Valk Paul,
Vaz Frédéric M,
Yeh SyunRu,
Geeraerts Zachary,
Dijkhuis Annemiek,
Vught Lonneke,
Bugiani Marianna,
Lutter René
Publication year - 2022
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5842
Subject(s) - quinolinic acid , aryl hydrocarbon receptor , kynurenine , indoleamine 2,3 dioxygenase , programmed cell death , apoptosis , pathological , medicine , immunology , biology , tryptophan , biochemistry , amino acid , gene , transcription factor
COVID‐19 is a pandemic with high morbidity and mortality. In an autopsy cohort of COVID‐19 patients, we found extensive accumulation of the tryptophan degradation products 3‐hydroxy‐anthranilic acid and quinolinic acid in the lungs, heart, and brain. This was not related to the expression of the tryptophan‐catabolizing indoleamine 2,3‐dioxygenase (IDO)‐1, but rather to that of its isoform IDO‐2, which otherwise is expressed rarely. Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death. Markers of apoptosis and severe cellular stress were associated with IDO‐2 expression in large areas of lung and heart tissue, whereas affected areas in brain were more restricted. Analyses of tissue, cerebrospinal fluid, and sequential plasma samples indicate early initiation of the kynurenine/aryl‐hydrocarbon receptor/IDO‐2 axis as a positive feedback loop, potentially leading to severe COVID‐19 pathology. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd on behalf of The Pathological Society of Great Britain and Ireland.