Indoleamine 2, 3‐dioxygenase (IDO)‐1 and IDO‐2 activity and severe course of COVID‐19. Issue 3 (10th January 2022)

• Record Type: Journal Article
• Authors: Guo, Lihui; Schurink, Bernadette; Roos, Eva; Nossent, Esther J; Duitman, Jan Willem; Vlaar, Alexander PJ; van der Valk, Paul; Vaz, Frédéric M; Yeh, Syun‐Ru; Geeraerts, Zachary; Dijkhuis, Annemiek; van Vught, Lonneke; Bugiani, Marianna; Lutter, René
• Other Names: van Agtmael Michiel investigator.; Algera Anne Geke investigator.; Appelman Brent investigator.; van Baarle Frank investigator.; Bax Diane investigator.; Beudel Martijn investigator.; Bogaard Harm Jan investigator.; Bomers Marije investigator.; Bonta Peter investigator.; Bos Lieuwe investigator.; Botta Michela investigator.; de Brabander Justin investigator.; Bree Godelieve investigator.; de Bruin Sanne investigator.; Bugiani Marianna investigator.; Bulle Esther investigator.; Chouchane Osoul investigator.; Cloherty Alex investigator.; Buis Buis T.P. investigator.; de Rotte Maurits C.F.J. investigator.; Dijkstra Mirjam investigator.; Dongelmans Dave A. investigator.; Dujardin Romein W.G. investigator.; Elbers Paul investigator.; Fleuren Lucas investigator.; Geerlings Suzanne investigator.; Geijtenbeek Theo investigator.; Girbes Armand investigator.; Goorhuis Bram investigator.; Grobusch Martin P. investigator.; Hafkamp Florianne investigator.; Hagens Laura investigator.; Hamann Jorg investigator.; Hamann Jorg investigator.; Harris Vanessa investigator.; Hemke Robert investigator.; Hermans Sabine M. investigator.; Heunks Leo investigator.; Hollmann Markus investigator.; Horn Janneke investigator.; Hovius Joppe W. investigator.; de Jong Menno D. investigator.; Koning Rutger investigator.; Lim Endry H.T. investigator.; van Mourik Niels investigator.; Nellen Jeannine investigator.; Nossent Esther J. investigator.; Paulus Frederique investigator.; Peters Edgar investigator.; Piña-Fuentes Dan A.I. investigator.; van der Poll Tom investigator.; Preckel Bennedikt investigator.; Prins Jan M. investigator.; Raasveld Jorinde investigator.; Reijnders Tom investigator.; Schinkel Michiel investigator.; Schrauwen Femke A.P. investigator.; Schultz Marcus J. investigator.; Schuurmans Alex investigator.; Schuurmans Jaap investigator.; Sigaloff Kim investigator.; Slim Marleen A. investigator.; Smit Marry investigator.; Stijnis Cornelis S. investigator.; Stilma Willemke investigator.; Teunissen Charlotte investigator.; Thoral Patrick investigator.; Tsonas Anissa M. investigator.; Tsonas Anissa investigator.; van der Valk Marc investigator.; Veelo Denise investigator.; Volleman Carolien investigator.; de Vries Heder investigator.; Vught Lonneke A. investigator.; van Vugt Michèle investigator.; Wouters Dorien investigator.; Zwinderman A. H (Koos) investigator.; Brouwer Matthijs C. investigator.; Wiersinga W. Joost investigator.; Vlaar Alexander P.J. investigator.; van de Beek Diederik investigator.;
• Is Part Of: Journal of pathology. Volume 256:Issue 3(2022)
• Page Start: 256
• Page End: 261
• Publication Date: 2022-01-10
• Subjects: tryptophan -- apoptosis -- autophagy -- innate_immune_response -- lungs -- brain -- heart -- skeletal_muscle -- nucleus_of_cranial_nerve_X; Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.5842
• Languages: English
• ISSNs: 0022-3417

Abstract

Abstract: 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.