Irini Sereti1, Alison J Rodger, Martyn A French. 1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. isereti@mail.nih.gov
Abstract
PURPOSE OF REVIEW: Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening or unmasking of an infection or neoplasm in HIV-1-infected patients shortly after antiretroviral therapy (ART) initiation. New insights into the pathogenesis of IRIS may help identify biomarkers that could be useful in predicting or diagnosing IRIS. RECENT FINDINGS: Studies of immunopathogenesis have shown a signification activation of both innate and adaptive immune responses with elevation of plasma or serum chemokines and cytokines. Markers of inflammation such as C-reactive protein, interferon-inducible protein 10 or interferon γ may be helpful as predictors of IRIS events. In addition, tuberculosis (TB)-associated IRIS is associated with a prominent Th1 response that can be heightened even prior to ART initiation in cases of unmasking TB, and may assist in early diagnosis. Large prospective studies are needed to elucidate the predictive and diagnostic value of IRIS biomarkers and advance them to the clinic. SUMMARY: Reversal of immunosuppression by ART leads to exaggerated pathogen-specific immune responses (known as IRIS) that appear to be primed prior to therapy. Inflammatory markers, chemokines and cytokines that signify innate and adaptive immune activation are biomarkers that could prove of clinical value after appropriate validation.
PURPOSE OF REVIEW: Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening or unmasking of an infection or neoplasm in HIV-1-infectedpatients shortly after antiretroviral therapy (ART) initiation. New insights into the pathogenesis of IRIS may help identify biomarkers that could be useful in predicting or diagnosing IRIS. RECENT FINDINGS: Studies of immunopathogenesis have shown a signification activation of both innate and adaptive immune responses with elevation of plasma or serum chemokines and cytokines. Markers of inflammation such as C-reactive protein, interferon-inducible protein 10 or interferon γ may be helpful as predictors of IRIS events. In addition, tuberculosis (TB)-associated IRIS is associated with a prominent Th1 response that can be heightened even prior to ART initiation in cases of unmasking TB, and may assist in early diagnosis. Large prospective studies are needed to elucidate the predictive and diagnostic value of IRIS biomarkers and advance them to the clinic. SUMMARY: Reversal of immunosuppression by ART leads to exaggerated pathogen-specific immune responses (known as IRIS) that appear to be primed prior to therapy. Inflammatory markers, chemokines and cytokines that signify innate and adaptive immune activation are biomarkers that could prove of clinical value after appropriate validation.
Authors: Joseph R Maxwell; Rajwardhan Yadav; Robert J Rossi; Carl E Ruby; Andrew D Weinberg; Hector L Aguila; Anthony T Vella Journal: J Immunol Date: 2006-07-01 Impact factor: 5.422
Authors: David B Clifford; Andrea De Luca; Andrea DeLuca; David M Simpson; Gabriele Arendt; Gavin Giovannoni; Avindra Nath Journal: Lancet Neurol Date: 2010-04 Impact factor: 44.182
Authors: Elias A Said; Franck P Dupuy; Lydie Trautmann; Yuwei Zhang; Yu Shi; Mohamed El-Far; Brenna J Hill; Alessandra Noto; Petronela Ancuta; Yoav Peretz; Simone G Fonseca; Julien Van Grevenynghe; Mohamed R Boulassel; Julie Bruneau; Naglaa H Shoukry; Jean-Pierre Routy; Daniel C Douek; Elias K Haddad; Rafick-Pierre Sekaly Journal: Nat Med Date: 2010-03-07 Impact factor: 53.440
Authors: N A Foudraine; E Hovenkamp; D W Notermans; P L Meenhorst; M R Klein; J M Lange; F Miedema; P Reiss Journal: AIDS Date: 1999-02-04 Impact factor: 4.177
Authors: Julian H Elliott; Khol Vohith; Sarun Saramony; Chin Savuth; Chan Dara; Chel Sarim; Sarah Huffam; Robert Oelrichs; Pouv Sophea; Vonthanak Saphonn; John Kaldor; David A Cooper; Mean Chhi Vun; Martyn A French Journal: J Infect Dis Date: 2009-12-01 Impact factor: 5.226
Authors: Anne Bourgarit; Guislaine Carcelain; Valerie Martinez; Caroline Lascoux; Veronique Delcey; Brigitte Gicquel; Eric Vicaut; Philippe H Lagrange; Daniel Sereni; Brigitte Autran Journal: AIDS Date: 2006-01-09 Impact factor: 4.177
Authors: Hans Lindå; Anders von Heijne; Eugene O Major; Caroline Ryschkewitsch; Johan Berg; Tomas Olsson; Claes Martin Journal: N Engl J Med Date: 2009-09-10 Impact factor: 91.245
Authors: Graeme Meintjes; Katalin Andrea Wilkinson; Molebogeng Xheeda Rangaka; Keira Skolimowska; Kerryn van Veen; Musaed Abrahams; Ronnett Seldon; Dominique J Pepper; Kevin Rebe; Priscilla Mouton; Gilles van Cutsem; Mark Patrick Nicol; Gary Maartens; Robert John Wilkinson Journal: Am J Respir Crit Care Med Date: 2008-08-28 Impact factor: 21.405
Authors: Denise C Hsu; Kimberly F Faldetta; Luxin Pei; Virginia Sheikh; Netanya S Utay; Gregg Roby; Adam Rupert; Anthony S Fauci; Irini Sereti Journal: Clin Infect Dis Date: 2015-09-22 Impact factor: 9.079
Authors: Yolanda D Mahnke; Jamieson H Greenwald; Rebecca DerSimonian; Gregg Roby; Lis R V Antonelli; Alan Sher; Mario Roederer; Irini Sereti Journal: Blood Date: 2012-01-04 Impact factor: 22.113
Authors: Aurelie Gouel-Cheron; Martha Nason; Adam Rupert; Virginia Sheikh; Greg Robby; Gary A Fahle; Irini Sereti Journal: Open Forum Infect Dis Date: 2020-01-11 Impact factor: 3.835
Authors: Maura Manion; Dimana Dimitrova; Luxin Pei; Juan Gea-Banacloche; Adrian Zelazny; Andrea Lisco; Christa Zerbe; Alexandra F Freeman; Steven M Holland; Christopher G Kanakry; Jennifer A Kanakry; Irini Sereti Journal: Clin Infect Dis Date: 2020-02-03 Impact factor: 9.079
Authors: Shruthi Ravimohan; Neo Tamuhla; Andrew P Steenhoff; Rona Letlhogile; Didimalang Kgomotso Makutu; Kebatshabile Nfanyana; Tumelo Rantleru; Ann Tierney; Kelebogile Nkakana; Adam B Schwartz; Robert Gross; Rob Roy Macgregor; Scarlett L Bellamy; Ian Frank; Drew Weissman; Gregory P Bisson Journal: J Infect Dis Date: 2013-08-01 Impact factor: 5.226
Authors: Philip M Grant; Lauren Komarow; Michael M Lederman; Savita Pahwa; Andrew R Zolopa; Janet Andersen; David M Asmuth; Sridevi Devaraj; Richard B Pollard; Aaron Richterman; Sudheesh Kanthikeel; Irini Sereti Journal: J Infect Dis Date: 2012-09-21 Impact factor: 5.226