TY - JOUR
T1 - Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19
AU - Amsterdam UMC Covid-19 Biobank
AU - Guo, Lihui
AU - Roos, Eva
AU - Duitman, Jan Willem
AU - Vlaar, Alexander P J
AU - van der Valk, Paul
AU - Vaz, Frédéric M
AU - Dijkhuis, Annemiek
AU - van Vught, Lonneke
AU - Lutter, René
AU - Appelman, Brent
AU - Beudel, Martijn
AU - Bonta, Peter
AU - Bos, Lieuwe
AU - Botta, Michela
AU - de Brabander, Justin
AU - de Bruin, Sanne
AU - Bulle, Esther
AU - Chouchane, Osoul
AU - de Rotte, Maurits C F J
AU - Dijkstra, Mirjam
AU - Dongelmans, Dave A
AU - Dujardin, Romein W G
AU - Elbers, Paul
AU - Geerlings, Suzanne
AU - Grobusch, Martin P
AU - Hafkamp, Florianne
AU - Hagens, Laura
AU - Harris, Vanessa
AU - Hemke, Robert
AU - Hermans, Sabine M
AU - Hollmann, Markus
AU - Horn, Janneke
AU - Hovius, Joppe W
AU - de Jong, Menno D
AU - Koning, Rutger
AU - Lim, Endry H T
AU - van Mourik, Niels
AU - Paulus, Frederique
AU - Piña-Fuentes, Dan A I
AU - van der Poll, Tom
AU - Prins, Jan M
AU - Raasveld, Jorinde
AU - Reijnders, Tom
AU - Schinkel, Michiel
AU - Schrauwen, Femke A P
AU - Schultz, Marcus J
AU - Schuurmans, Jaap
AU - Sigaloff, Kim
AU - Slim, Marleen A
AU - Smit, Marry
AU - Stilma, Willemke
AU - Tsonas, Anissa
AU - Tsonas, Anissa
AU - van der Valk, Marc
AU - Veelo, Denise
AU - Volleman, Carolien
AU - van Vugt, Michèle
AU - Brouwer, Matthijs C
AU - Wiersinga, W Joost
AU - Vlaar, Alexander P J
AU - van de Beek, Diederik
AU - also on behalf of the Amsterdam UMC COVID-19 Biobank Study Group
AU - Schurink, Bernadette
AU - Nossent, Esther J
AU - Yeh, Syun-Ru
AU - Bugiani, Marianna
AU - van Agtmael, Michiel
AU - van Baarle, Frank
AU - Bogaard, Harm Jan
AU - Bomers, Marije
AU - Bugiani, Marianna
AU - Fleuren, Lucas
AU - Girbes, Armand
AU - Heunks, Leo
AU - Nossent, Esther J
AU - Peters, Edgar
AU - Stijnis, Cornelis S
AU - Teunissen, Charlotte
AU - Thoral, Patrick
AU - de Vries, Heder
N1 - Publisher Copyright: © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85122689838&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34859884
UR - http://www.scopus.com/inward/record.url?scp=85122689838&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/path.5842
DO - https://doi.org/10.1002/path.5842
M3 - Article
C2 - 34859884
SN - 0022-3417
VL - 256
JO - Journal of pathology
JF - Journal of pathology
IS - 3
ER -