Article
Immunology
Caian L. Vinhaes, Virginia Sheikh, Deivide Oliveira-de-Souza, Jing Wang, Adam Rupert, Gregg Roby, Maria B. Arriaga, Kiyoshi F. Fukutani, Fred Sawe, Doug Shaffer, Jintanat Ananworanich, Nittaya Phanuphak, Bruno B. Andrade, Irini Sereti
Summary: The study found that systemic inflammatory profiles in people with severe immunosuppression can predict the development of immune reconstitution inflammatory syndrome (IRIS). By developing a composite score incorporating various biomarkers, including interleukin-6, IL-10, IL-27, sCD14, interferon-gamma, tumor necrosis factor-alpha, hyaluronic acid, D-dimer, body mass index, and hemoglobin, accurate predictions of IRIS occurrence and death risk can be made.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Immunology
Joseph M. Rocco, Elizabeth Laidlaw, Frances Galindo, Megan Anderson, Ornella Sortino, Safia Kuriakose, Andrea Lisco, Maura Manion, Irini Sereti
Summary: People with HIV and mycobacterial infections may develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy. The pathophysiology of mycobacterial-IRIS overlaps with primary hemophagocytic lymphohistiocytosis (pHLH). By evaluating protein-altering variants in genes associated with HLH, it was found that 23.2% of IRIS patients had these variants, compared to only 3.8% of those without IRIS. These findings suggest a possible genetic component in the risk of mycobacterial IRIS in people with HIV and mycobacterial infections.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Joseph M. Rocco, Elizabeth Laidlaw, Frances Galindo, Megan Anderson, Adam Rupert, Jeanette Higgins, Ornella Sortino, Ana M. Ortega-Villa, Virginia Sheikh, Gregg Roby, Safia Kuriakose, Andrea Lisco, Maura Manion, Irini Sereti
Summary: Severe mycobacterial IRIS in HIV can cause secondary HLH driven by pathologic IFN gamma production and T-cell activation, leading to worse outcomes. Increased ferritin, anemia, CXCL9, and sCD25 associate with this phenotype and may be used for risk stratification and treatment optimization.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Microbiology
Marina Nosik, Konstantin Ryzhov, Irina Rymanova, Alexandr Sobkin, Alexey Kravtchenko, Ulyana Kuimova, Vadim Pokrovsky, Vitaly Zverev, Oxana Svitich
Summary: Coinfection with HIV/TB suppresses both Th1 and Th2 immune responses, leading to delayed immune recovery and potentially providing IL-6 as a potential marker for early detection of TB infection in HIV-infected individuals, with IL-1Ra emerging as a potential predictive biomarker for TB-IRIS development and treatment outcomes.
Article
Immunology
Stanley Kimbung Mbandi, Hannah Painter, Adam Penn-Nicholson, Asma Toefy, Mzwandile Erasmus, Willem A. Hanekom, Thomas J. Scriba, Rachel P. J. Lai, Suzaan Marais, Helen A. Fletcher, Graeme Meintjes, Robert J. Wilkinson, Mark F. Cotton, Savita Pahwa, Mark J. Cameron, Elisa Nemes
Summary: Immune reconstitution inflammatory syndrome (IRIS) is a complication of antiretroviral therapy (ART) in patients with advanced HIV, but its pathogenesis is uncertain. This study found that immune-based blood transcriptomic signatures (RISK6 and Sweeney3) have the potential to predict and diagnose IRIS in HIV+ children and adults.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Ran Tao, Xiaorong Peng, Xiang Liu, Junwei Su, Guanjing Lang, Ying Huang, Yafei Zhang, Biao Zhu
Summary: Cryptococcal meningitis (CM) is a common opportunistic infection in HIV patients. This study reports two cases of CM-associated immune reconstitution inflammatory syndrome (IRIS) treated with lenalidomide, which resulted in rapid clinical remission and improved cognitive function. The study also suggests that lenalidomide may improve cognitive function by regulating intracranial inflammation through multiple pathways, not just by TNF-α blocking.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Article
Microbiology
Polidy Pean, Yoann Madec, Eric Nerrienet, Laurence Borand, Didier Laureillard, Marcelo Fernandez, Olivier Marcy, Daniel Scott-Algara, CAMELIA Study Team
Summary: The aim of this study was to evaluate the reconstitution of NK cells in HIV-infected patients with TB-IRIS compared to those without IRIS. The results showed that NK cell reconstitution appeared to be better in TB-IRIS subjects. However, the development of IRIS does not appear to affect the NK cell reconstitution in HIV and TB-infected individuals.
Article
Immunology
Luxin Pei, Kiyoshi F. Fukutani, Rafael Tiburcio, Adam Rupert, Eric W. Dahlstrom, Frances Galindo, Elizabeth Laidlaw, Andrea Lisco, Maura Manion, Bruno B. Andrade, Irini Sereti
Summary: The study identified metabolic disturbances in IRIS before and during the event, linking oxidative stress, tryptophan pathway, and lipid signaling with IRIS development. Metabolic pathways of lipids and amino acids were significantly associated with inflammatory biomarkers like IL-12p70 and IL-8 during the IRIS event, suggesting the impact of cellular metabolism on immune cell activation and vice versa.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biology
Caian L. Vinhaes, Mariana Araujo-Pereira, Rafael Tiburcio, Juan M. Cubillos-Angulo, Fernanda O. Demitto, Kevan M. Akrami, Bruno B. Andrade
Summary: Antiretroviral therapy (ART) has greatly improved the care of people living with HIV, but can lead to immune reconstitution inflammatory syndrome (IRIS), causing significant morbidity and mortality. There are still gaps in understanding IRIS pathogenesis and optimizing therapeutic strategies.
Article
Medicine, General & Internal
Yanli Wang, Xuyong Lin, Yuji Li, Ying Wen
Summary: Multiple intestinal perforations are a severe complication of enteric CMV infection in HIV patients, sometimes related to IRIS after starting ART. Cases typically present shortly after ART initiation without prodromal gastrointestinal symptoms. Intestinal perforations are lethal, highlighting the importance of early detection and surgical intervention.
Article
Microbiology
Silvia Lucena Lage, Chun-Shu Wong, Eduardo Pinheiro Amaral, Daniel Sturdevant, Denise C. Hsu, Adam Rupert, Eleanor M. P. Wilson, S. Sonia Qasba, Nuha Sultana Naqvi, Elizabeth Laidlaw, Andrea Lisco, Maura Manion, Irini Sereti
Summary: In TB-IRIS patients, inflammasome activation on monocytes is associated with pro-inflammatory cytokine levels, while complement deposition may lead to a positive feedback loop in the inflammatory responses observed.
Article
Immunology
Chunmei Qu, Nannan Xu, Dehong Niu, Sai Wen, Hui Yang, Shanshan Wang, Gang Wang
Summary: Human brucellosis is a prevalent zoonotic disease with similarities in pathogenesis to Mycobacterium tuberculosis (MTB) infection. Immune reconstitution inflammatory syndrome (IRIS) has been reported in cases of MTB infection but not in brucellosis cases. We present a case of a 40-year-old male who initially showed improvement after anti-Brucella therapy but later developed symptoms exacerbation and a paravertebral abscess, suggestive of IRIS. Treatment with corticosteroids in addition to anti-Brucella therapy resulted in resolution of the abscess and complete symptom relief. Our case highlights the importance of recognizing the possible occurrence of IRIS in patients with brucellosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Eduarda Grinsztejn, Sandra Wagner Cardoso, Luciane Velasque, Brenda Hoagland, Desiree Gomes dos Santos, Carolina Coutinho, Simone da Costa Cruz Silva, Sandro Coutinho Nazer, Ana Cristina Garcia Ferreira, Jessica Castilho, Beatriz Grinsztejn, Valdilea G. Veloso
Summary: Initiating antiretroviral therapy (ART) early during acute HIV infection (AHI) may help mitigate immune damage. Efforts to diagnose HIV and initiate ART during AHI are critical to amplify the benefits of ART.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2023)
Article
Immunology
Shuangjun Liu, Feng Huo, Guorui Dai, Jie Wu, Maoquan Qin, Huawei Mao, Quan Wang
Summary: This case report describes a patient who developed immune reconstitution inflammatory syndrome (IRIS) after hematopoietic stem cell transplantation, following severe disseminated infection caused by bacillus Calmette-Guerin (BCG) vaccine. The patient experienced complications including veno-occlusive disease and acute graft-versus-host disease post-transplant, with symptoms of IRIS emerging after immunosuppressants were withdrawn.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Ophthalmology
Ines Hernanz, Andrea Alvear-Torres, Cristina Serrano del Castillo, Olga Sanchez-Pernaute, Sheila Recuero, Fredeswinda Romero-Bueno, Nelida Munoz, Ester Carreno
Summary: A retrospective review of HIV patients with noninfectious uveitis found that uveitis could be the initial manifestation of immune-mediated disorders in patients with well-controlled HIV infection, and immunosuppression appeared to be a safe therapeutic option.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2022)
Article
Immunology
Ying Zhao, Rulan Griesel, Zaayid Omar, Bryony Simmons, Andrew Hill, Gert van Zyl, Claire Keene, Gary Maartens, Graeme Meintjes
Summary: This study evaluated the need for an initial dolutegravir dose adjustment in adults switching from first-line TEE treatment to TLD. The results showed that in patients with unsuppressed HIV-1 RNA levels and substantial baseline resistance to nucleoside reverse transcriptase inhibitors, a high proportion achieved virologic suppression without the need for an initial dolutegravir dose adjustment.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Immunology
Angharad G. Davis, Sean Wasserman, Cari Stek, Mpumi Maxebengula, C. Jason Liang, Stephani Stegmann, Sonya Koekemoer, Amanda Jackson, Yakub Kadernani, Marise Bremer, Remy Daroowala, Saalikha Aziz, Rene Goliath, Louise Lai Sai, Thandi Sihoyiya, Paolo Denti, Rachel P. J. Lai, Thomas Crede, Jonathan Naude, Patryk Szymanski, Yakoob Vallie, Ismail Abbas Banderker, Muhammed S. Moosa, Peter Raubenheimer, Sally Candy, Curtis Offiah, Gerda Wahl, Isak Vorster, Gary Maartens, John Black, Graeme Meintjes, Robert J. Wilkinson
Summary: In this study, it was demonstrated that high-dose rifampicin and adjunctive linezolid is safe in adult HIV-associated tuberculous meningitis patients. Larger studies are needed to evaluate the potential toxicity of high-dose aspirin and its benefits on morbidity and mortality.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Infectious Diseases
Mary-Ann Davies, Erna Morden, Petro Rousseau, Juanita Arendse, Jamy-Lee Bam, Linda Boloko, Keith Cloete, Cheryl Cohen, Nicole Chetty, Pierre Dane, Alexa Heekes, Nei-Yuan Hsiao, Mehreen Hunter, Hannah Hussey, Theuns Jacobs, Waasila Jassat, Saadiq Kariem, Reshma Kassanjee, Inneke Laenen, Sue Le Roux, Richard Lessells, Hassan Mahomed, Deborah Maughan, Graeme Meintjes, Marc Mendelson, Ayanda Mnguni, Melvin Moodley, Katy Murie, Jonathan Naude, Ntobeko A. B. Ntusi, Masudah Paleker, Arifa Parker, David Pienaar, Wolfgang Preiser, Hans Prozesky, Peter Raubenheimer, Liezel Rossouw, Neshaad Schrueder, Barry Smith, Mariette Smith, Wesley Solomon, Greg Symons, Jantjie Taljaard, Sean Wasserman, Robert J. Wilkinson, Milani Wolmarans, Nicole Wolter, Andrew Boulle
Summary: The clinical severity of Omicron BA.4/BA.5 infection was compared to BA.1 and earlier variant infections, and it was found that vaccination and previous infection were protective against disease severity.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Review
Pharmacology & Pharmacy
Jacob A. M. Stadler, Gary Maartens, Graeme Meintjes, Sean Wasserman
Summary: Shorter and fully oral regimens with new and repurposed drugs have become the first-choice treatment for drug-resistant tuberculosis. Clofazimine, a repurposed drug used in leprosy treatment, has shown promising results in treating drug-resistant tuberculosis. However, the safety, dosing considerations, adverse effects, and resistance mechanisms of clofazimine still need further research and evaluation.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Kevin Ng, Jesse Boumelha, Katey S. S. Enfield, Jorge L. Almagro, Hongui M. Cha, Oriol Pich, Takahiro Karasaki, David Moore, Roberto Salgado, Monica Sivakumar, George Young, Miriam L. Molina-Arcas, Sophie de Carne Trecesson, Panayiotis Anastasiou, Annika C. Fendler, Lewis Au, Scott T. C. Shepherd, Carlos Martinez-Ruiz, Clare Puttick, James R. M. Black, Thomas B. K. Watkins, Hyemin Kim, Seohee Shim, Nikhil Faulkner, Jan A. Attig, Selvaraju Veeriah, Neil J. Magno, Sophia T. Ward, Alexander Frankell, Maise Al Bakir, Emilia Lim, Mark Hill, Gareth Wilson, Daniel Cook, Nicolai Birkbak, Axel Behrens, Nadia Yousaf, Sanjay Popat, Allan Hackshaw, TRACERx Consortium, CAPTURE Consortium, Crispin T. Hiley, Kevin Litchfield, Nicholas McGranahan, Mariam Jamal-Hanjani, James Larkin, Se-Hoon Lee, Samra Turajlic, Charles Swanton, Julian Downward, George Kassiotis
Summary: This study reveals that lung adenocarcinomas in both humans and mice elicit local germinal center responses and tumour-binding antibodies, with endogenous retrovirus (ERV) envelope glycoproteins as the dominant anti-tumour antibody target. ERV-targeting B cell responses are enhanced by immune checkpoint blockade (ICB) and targeted inhibition of KRAS(G12C). ERV-reactive antibodies have anti-tumour activity and improve survival in a mouse model, and ERV expression predicts the response to ICB in human lung adenocarcinoma. Furthermore, the study demonstrates that effective immunotherapy in the mouse model requires CXCL13-dependent tertiary lymphoid structure (TLS) formation, and therapeutic CXCL13 treatment enhances anti-tumour immunity and synergizes with ICB. These findings provide a potential mechanistic basis for the association between TLS and immunotherapy response.
Article
Microbiology
Michaela Zwyer, Liliana Rutaihwa, Etthel Windels, Jerry Hella, Fabrizio Menardo, Mohamed Sasamalo, Gregor Sommer, Lena Schmulling, Sonia Borrell, Miriam C. Reinhard, Anna Dotsch, Hellen Hiza, Christoph D. Stritt, George Sikalengo, Lukas Fenner, Bouke De Jong, Midori Kato-Maeda, Levan Jugheli, Joel Ernst, Stefan Niemann, Leila Jeljeli, Marie Ballif, Matthias Egger, Niaina J. Rakotosamimanana, Dorothy Yeboah-Manu, Prince Asare, Bijaya Malla, Horng Yunn Dou, Nicolas Zetola, Robert Wilkinson, Helen Cox, E. Jane Carter, Joachim Gnokoro, Marcel Yotebieng, Eduardo Gotuzzo, Alash'le Abimiku, Anchalee Avihingsanon, Zhi Ming Xu, Jacques Fellay, Damien Portevin, Klaus Reither, Tanja Stadler, Sebastien Gagneux, Daniela Brites
Summary: In Dar es Salaam, Tanzania, the tuberculosis epidemic is dominated by multiple Mycobacterium tuberculosis complex (MTBC) genotypes introduced from different parts of the world. These genotypes differ in transmission rates and infectious period duration, but have similar overall fitness. The high prevalence of the L3.1.1 genotype is attributed to its early introduction and high transmission rate.
Correction
Immunology
Elsa Du Bruyn, Sheena Ruzive, Patrick Howlett, Maddalena Cerrone, Ashley J. Jacobs, Cecilia Lindestam S. Arlehamn, Alessandro Sette, Alan Sher, Katrin D. Mayer-Barber, Daniel L. Barber, Bongani Mayosi, Mpiko Ntsekhe, Robert J. Wilkinson, Catherine Riou
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Mariana Araujo-Pereira, Charlotte Schutz, Beatriz Barreto-Duarte, David Barr, Klauss Villalva-Serra, Caian L. Vinhaes, Amy Ward, Graeme Meintjes, Bruno B. Andrade
Summary: This study aimed to investigate the relationship between anemia, systemic inflammatory profile, dissemination of tuberculosis (TB), and death. Through the analysis of 496 HIV patients, it was found that severe anemia is associated with increased systemic inflammation, higher TB dissemination score, and greater risk of death.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Muki Shehu Shey, Avuyonke Balfour, Nomawethu Masina, Abulele Bekiswa, Charlotte Schutz, Rene Goliath, Rachel Dielle, Patrick DMC. Katoto, Katalin Andrea Wilkinson, David Lewinsohn, Deborah Anne Lewinsohn, Graeme Meintjes
Summary: In this study, it was found that individuals who showed resistance to Mycobacterium tuberculosis (Mtb) infection despite sustained exposure had lower secretion of IFN-gamma, a cytokine traditionally associated with Mtb infection. However, these individuals showed similar secretion levels of other immune response-related cytokines and chemokines, indicating their ability to mount non-IFN-gamma immune responses to Mtb infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Edgar Gonzalez-Rodriguez, Mia Zol-Hanlon, Ganka Bineva-Todd, Andrea Marchesi, Mark Skehel, Keira E. Mahoney, Chloe Roustan, Annabel Borg, Lucia Di Vagno, Svend Kjaer, Antoni G. Wrobel, Donald J. Benton, Philipp Nawrath, Sabine L. Flitsch, Dhira Joshi, Andres Manuel Gonzalez-Ramirez, Katalin A. Wilkinson, Robert J. Wilkinson, Emma C. Wall, Ramon Hurtado-Guerrero, Stacy A. Malaker, Benjamin Schumann
Summary: The polybasic cleavage motif for the protease furin is a major factor in human viral transmission of SARS-CoV-2 spike. Variants of concern (VOCs) have extensive mutations in the region preceding this motif. Besides furin, spikes from these variants rely on other proteases such as TMPRSS2 for maturation. Glycans near the cleavage site have implications for proteolytic processing and the effects of variant-borne mutations.
ACS CENTRAL SCIENCE
(2023)
Article
Immunology
Robert J. Wilkinson, Joseph Donovan, Guy E. Thwaites, Reinout van Crevel, Sean Wasserman
Article
Genetics & Heredity
Elouise E. Kroon, Wilian Correa-Macedo, Rachel Evans, Allison Seeger, Lize Engelbrecht, Jurgen A. Kriel, Ben Loos, Naomi Okugbeni, Marianna Orlova, Pauline Cassart, Craig J. Kinnear, Gerard C. Tromp, Marlo Moller, Robert J. Wilkinson, Anna K. Coussens, Erwin Schurr, Eileen G. Hoal
Summary: Persons living with HIV who never develop tuberculosis and show no immune sensitization to Mycobacterium tuberculosis have been identified as HIV+ persistently TB, tuberculin, and IGRA negative (HITTIN). In this study, their neutrophil Mtb infection response was compared to PLWH with no TB history but who test persistently IGRA positive and tuberculin positive (HIT). The HITTIN group exhibited distinct innate mechanisms in response to Mtb infection.
Review
Immunology
Petro Booysen, Katalin A. Wilkinson, Dylan Sheerin, Robyn Waters, Anna K. Coussens, Robert J. Wilkinson
Summary: SARS-CoV-2 and Mycobacterium tuberculosis are major infectious causes of death, and co-infected patients have increased mortality rates. The immune interaction between these two pathogens impacts the outcomes of co-infected individuals. Both SARS-CoV-2 and Mtb modulate immune responses in cells such as monocytes, macrophages, neutrophils, and T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Infectious Diseases
S. Veenstra, M. N. Porter, B. N. Thwala, N. Pillay, M. A. Panieri, J. van der Westhuizen, E. J. Phillips, G. Meintjes, S. Dlamini, R. J. Lehloenya, J. Peter
Summary: Severe cutaneous adverse reactions among patients with HIV-associated tuberculosis (TB) result in high mortality and treatment complexity. However, with good care, TB treatment can be successfully completed and immune recovery is good.
JOURNAL OF CLINICAL TUBERCULOSIS AND OTHER MYCOBACTERIAL DISEASES
(2023)
Article
Microbiology
Eduardo P. Amaral, Sivaranjani Namasivayam, Artur T. L. Queiroz, Eduardo Fukutani, Kerry L. Hilligan, Kate Aberman, Logan Fisher, Caio Cesar B. Bomfim, Keith Kauffman, Jay Buchanan, Leslie Santuo, Pedro Henrique Gazzinelli-Guimaraes, Diego L. Costa, Mariane Araujo Teixeira, Beatriz Barreto-Duarte, Clarissa Gurgel Rocha, Monique Freire Santana, Marcelo Cordeiro-Santos, Daniel L. Barber, Robert J. Wilkinson, Igor Kramnik, Kazuhiko Igarashi, Thomas Scriba, Katrin D. Mayer-Barber, Bruno B. Andrade, Alan Sher
Summary: The transcription factor Bach1 plays a key role in regulating host resistance to Mycobacterium tuberculosis infection by influencing antioxidant gene expression, inhibiting lipid peroxidation, and reducing necrosis and bacterial loads in mice. Its deletion increases resistance to Mtb-induced cell death and improves survival, highlighting Bach1 as a crucial regulator of cellular and tissue necrosis in Mtb infection.
NATURE MICROBIOLOGY
(2023)
