Deivide Oliveira-de-Souza

Fundação Oswaldo Cruz

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Caian L. Vinhaes

Fundação Oswaldo Cruz

Bruno B. Andrade

Fundação Oswaldo Cruz

Kiyoshi F. Fukutani

Dartmouth College

Laura E. Via

National Institute of Allergy and Infectious Diseases

María B. Arriaga

Complexo Hospitalar Universitário Professor Edgard Santos

Nathella Pavan Kumar

National Institute of Research in Tuberculosis

Subash Babu

National Institutes of Health

Artur T. L. Queiroz

Fundação Oswaldo Cruz

Cecilia S. Lindestam Arleham

La Jolla Institute for Immunology

Sivaranjani Namasivayam

National Institutes of Health

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National Institutes of Health

National Institute of Allergy and Infectious Diseases

Fundação Oswaldo Cruz

Universidade Federal da Bahia

Faculdade de Tecnologia e Ciências

Vanderbilt University

Emory University

Government of the United States of America

Universidade Salvador

National Institute of Research in Tuberculosis

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An Inflammatory Composite Score Predicts Mycobacterial Immune Reconstitution Inflammatory Syndrome in People with Advanced HIV: A Prospective International Cohort Study

The Journal of Infectious Diseases (2020)

Caian L. Vinhaes Virginia Sheikh Deivide Oliveira-de-Souza Jing Wang Adam Rupert

Immune reconstitution inflammatory syndrome (IRIS) is a common cause of morbidity among people with human immunodeficiency virus (PWH) who initiate antiretroviral therapy (ART) with severe lymphopenia. Easily accessible tools that reliably predict emergence and elucidate pathogenesis of IRIS are needed to facilitate improved clinical management.Plasma levels of biomarkers were measured before ART initiation in a large multinational cohort of ART-naive PWH with severe immunosuppression (CD4+ count <100 cells/mm3) in United States, Kenya, and Thailand. We performed a series of multiparametric analyses of inflammatory and clinical biomarkers and developed a composite score merging relevant biomarkers for use in a prediction model.We identified a distinct baseline inflammatory profile and changes in inflammatory networks among biomarkers in participants who subsequently developed mycobacterial or viral IRIS. We also developed a composite score incorporating biomarkers associated with IRIS (interleukin-6 [IL-6], IL-10, IL-27, sCD14, interferon-γ, tumor necrosis factor-α, hyaluronic acid, D-dimer, body mass index, and hemoglobin) that accurately predicted mycobacterial IRIS and death in this cohort.Systemic inflammatory profiles in PWH with severe immunosuppression are predictive of IRIS. Composite scores for the prediction of mycobacterial IRIS and death could be useful for risk stratification in PWH and lymphopenia initiating ART.NCT00286767.

Immunosuppression

Procalcitonin

10.1093/infdis/jiaa484

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Citations (19)

Aging increases the systemic molecular degree of inflammatory perturbation in patients with tuberculosis

bioRxiv (Cold Spring Harbor Laboratory) (2020)

Deivide Oliveira-de-Souza Caian L. Vinhaes María B. Arriaga Nathella Pavan Kumar Artur T. L. Queiroz

Abstract Tuberculosis (TB) in a chronic infection that can affect individuals of all ages. The description of determinants of immunopathogenesis in TB is a field of tremendous interest due to the perspective of finding a reliable host-directed therapy to reduce disease burden. The association between specific biomarker profiles related to inflammation and the diverse clinical disease presentations in TB has been extensively studied in adults. However, relatively scarce data on profiling the inflammatory responses in pediatric TB are available. Here, we employed the molecular degree of perturbation (MDP) score adapted to plasma biomarkers in two distinct databanks from studies that examined either adults or children presenting with pulmonary or extrapulmonary disease. We used multidimensional statistical analyses to characterize the impact of age on the overall changes in the systemic inflammation profiles in subpopulation of TB patients. Our findings indicated that TB results in significant increases in MDP values, with the highest values being detected in adult patients. Furthermore, there were unique differences in the biomarker perturbation patterns and the overall degree of inflammation according to disease site and age. Importantly, the molecular degree of perturbation was not influenced by sex. Our results revealed that aging is an important determinant of the differences in quality and magnitude of systemic inflammatory perturbation in distinct clinical forms of TB.

10.1101/2020.03.10.985697

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Citations (0)

Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: A prospective cohort study

Cytokine (2019)

Caian L. Vinhaes Deivide Oliveira-de-Souza Paulo S. Silveira-Mattos Betânia M. F. Nogueira Ruiru Shi

Mediator

Extrapulmonary tuberculosis

10.1016/j.cyto.2019.154759

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Citations (52)

Aging increases the systemic molecular degree of inflammatory perturbation in patients with tuberculosis

Scientific Reports (2020)

Deivide Oliveira-de-Souza Caian L. Vinhaes María B. Arriaga Nathella Pavan Kumar Artur T. L. Queiroz

Abstract Tuberculosis (TB) is a chronic infection that can affect individuals of all ages. The description of determinants of immunopathogenesis in TB is of tremendous interest due to the perspective of finding a reliable host-directed therapy to reduce disease burden. The association between specific biomarker profiles related to inflammation and the diverse clinical disease presentations in TB has been extensively studied in adults. However, relatively scarce data on profiling the inflammatory responses in pediatric TB are available. Here, we employed the molecular degree of perturbation (MDP) score adapted to plasma biomarkers in two distinct databanks from studies that examined either adults or children presenting with pulmonary or extrapulmonary disease. We used multidimensional statistical analyses to characterize the impact of age on the overall changes in the systemic inflammation profiles in subpopulation of TB patients. Our findings indicate that TB results in significant increases in molecular perturbation, with the highest values being detected in adult patients. Furthermore, there were unique differences in the biomarker perturbation patterns and the overall degree of inflammation according to disease site and age. Importantly, the molecular degree of perturbation was not influenced by sex. Our results revealed that aging is an important determinant of the differences in quality and magnitude of systemic inflammatory perturbation in distinct clinical forms of TB.

10.1038/s41598-020-68255-0

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Multifocal tuberculosis-associated immune reconstitution inflammatory syndrome – a case report of a complicated scenario

BMC Infectious Diseases (2019)

Gopalan Narendran Deivide Oliveira-de-Souza Caian L. Vinhaes Kevan Akrami Kiyoshi F. Fukutani

Tuberculosis (TB)-associated Immune reconstitution inflammatory syndrome (TB-IRIS) is an aberrant inflammatory response in TB patients with advanced human immunodeficiency virus coinfection, after antiretroviral therapy commencement. We present a rare case of a 51-year-old woman living with HIV who developed a series of TB-IRIS events occurring at multiple sites sequentially, highlighting the clinical complexity in diagnosis and management. This case illustrates how complicated a clinical scenario of successive TB-IRIS episodes can be, in terms of clinical management.

Medical microbiology

Parasitology

10.1186/s12879-019-4182-1

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Citations (6)

PD-1 blockade exacerbatesMycobacterium tuberculosisinfection in rhesus macaques

bioRxiv (Cold Spring Harbor Laboratory) (2020)

Keith D. Kauffman Shunsuke Sakai Nickiana E. Lora Sivaranjani Namasivayam Paul J. Baker

ABSTRACT Boosting immune cell function by targeting the co-inhibitory receptor PD-1 may have applications in the treatment of chronic infections. Here we examine the role of PD-1 during Mycobacterium tuberculosis (Mtb) infection of rhesus macaques. Animals treated with αPD-1 mAb developed worse disease and higher granuloma bacterial loads compared to isotype control treated monkeys. PD-1 blockade increased the number and functionality of granuloma Mtb-specific CD8 T cells. In contrast, Mtb-specific CD4 T cells in αPD-1 treated macaques were not increased in number or function in granulomas, upregulated high levels of CTLA-4 and exhibited reduced intralesional trafficking in live imaging studies. In granulomas of αPD-1 treated animals, multiple pro-inflammatory cytokines were elevated, and more cytokines correlated with bacterial loads, leading to the identification of a role for caspase 1 in the exacerbation of tuberculosis after PD-1 blockade. Lastly, increased Mtb bacterial loads after PD-1 blockade were found to associate with the composition of the intestinal microbiota prior to infection in individual macaques. Therefore, PD-1-mediated co-inhibition is required for control of Mtb infection in macaques, perhaps due to its role in dampening detrimental inflammation as well as allowing for normal CD4 T cell responses.

Isotype

10.1101/2020.08.05.237883

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Citations (1)

Differential Expression of Activation Markers by Mycobacterium tuberculosis-specific CD4+ T Cell Distinguishes Extrapulmonary From Pulmonary Tuberculosis and Latent Infection

Clinical Infectious Diseases (2019)

Paulo S. Silveira-Mattos Beatriz Barreto‐Duarte Beatriz Helena Baldez Vasconcelos Kiyoshi F. Fukutani Caian L. Vinhaes

Abstract Background Diagnosis of active tuberculosis (ATB) currently relies on detection of Mycobacterium tuberculosis (Mtb). Identifying patients with extrapulmonary TB (EPTB) remains challenging because microbiological confirmation is often not possible. Highly accurate blood-based tests could improve diagnosis of both EPTB and pulmonary TB (PTB) and timely initiation of anti-TB therapy. Methods A case-control study was performed using discriminant analyses to validate an approach using Mtb-specific CD4+T-cell activation markers in blood to discriminate PTB and EPTB from latent TB infection (LTBI) as well as EPTB from PTB in 270 Brazilian individuals. We further tested the effect of human immunodeficiency virus (HIV) coinfection on diagnostic performance. Frequencies of interferon-γ +CD4+T cells expressing CD38, HLADR, and/or Ki67 were assessed by flow cytometry. Results EPTB and PTB were associated with higher frequencies of CD4+T cells expressing CD38, HLADR, or Ki67 compared with LTBI (all P values < .001). Moreover, frequencies of HLADR+ (P = .03) or Ki67+ (P < .001) cells accurately distinguished EPTB from PTB. HIV infection did not affect the capacity of these markers to distinguish ATB from LTBI or EPTB from PTB. Conclusions Cell activation markers in Mtb-specific CD4+T cells distinguished ATB from LTBI and EPTB from PTB, regardless of HIV infection status. These parameters provide an attractive approach for developing blood-based diagnostic tests for both active and latent TB.

Extrapulmonary tuberculosis

10.1093/cid/ciz1070

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Citations (44)

The Interplay Between Systemic Inflammation, Oxidative Stress, and Tissue Remodeling in Tuberculosis

Antioxidants and Redox Signaling (2020)

Eduardo P. Amaral Caian L. Vinhaes Deivide Oliveira-de-Souza Betânia M. F. Nogueira Kevan Akrami

Significance: Excessive and prolonged proinflammatory responses are associated with oxidative stress, which is commonly observed during chronic tuberculosis (TB). Such condition favors tissue destruction and consequently bacterial spread. A tissue remodeling program is also triggered in chronically inflamed sites, facilitating a wide spectrum of clinical manifestations. Recent Advances: Since persistent and exacerbated oxidative stress responses have been associated with severe pathology, a number of studies have suggested that the inhibition of this augmented stress response by improving host antioxidant status may represent a reasonable strategy to ameliorate tissue damage in TB. Critical Issues: This review summarizes the interplay between oxidative stress, systemic inflammation and tissue remodeling, and its consequences in promoting TB disease. We emphasize the most important mechanisms associated with stress responses that contribute to the progression of TB. We also point out important host immune components that may influence the exacerbation of cellular stress and the subsequent tissue injury. Future Directions: Further research should reveal valuable targets for host-directed therapy of TB, preventing development of severe immunopathology and disease progression. Antioxid. Redox Signal. 34, 471-485.

Tissue Remodeling

Proinflammatory cytokine

10.1089/ars.2020.8124

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Citations (56)

Molecular degree of perturbation of plasma inflammatory markers associated with tuberculosis reveals distinct disease profiles between Indian and Chinese populations

Scientific Reports (2019)

Deivide Oliveira-de-Souza Caian L. Vinhaes María B. Arriaga Nathella Pavan Kumar Juan M. Cubillos-Angulo

Abstract Tuberculosis (TB) is a chronic inflammatory disease caused by Mycobacterium tuberculosis infection which causes tremendous morbidity and mortality worldwide. Clinical presentation of TB patients is very diverse and disease heterogeneity is associated with changes in biomarker signatures. Here, we compared at the molecular level the extent of individual inflammatory perturbation of plasma protein and lipid mediators associated with TB in patients in China versus India. We performed a cross-sectional study analyzing the overall degree of inflammatory perturbation in treatment-naïve pulmonary TB patients and uninfected individuals from India (TB: n = 97, healthy: n = 20) and China (TB: n = 100, healthy: n = 11). We employed the molecular degree of perturbation (MDP) adapted to plasma biomarkers to examine the overall changes in inflammation between these countries. M. tuberculosis infection caused a significant degree of molecular perturbation in patients from both countries, with higher perturbation detected in India. Interestingly, there were differences in biomarker perturbation patterns and the overall degree of inflammation. Patients with severe TB exhibited increased MDP values and Indian patients with this condition exhibited even higher degree of perturbation compared to Chinese patients. Network analyses identified IFN-α, IFN-β, IL-1RI and TNF-α as combined biomarkers that account for the overall molecular perturbation in the entire study population. Our results delineate the magnitude of the systemic inflammatory perturbation in pulmonary TB and reveal qualitative changes in inflammatory profiles between two countries with high disease prevalence.

10.1038/s41598-019-44513-8

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Citations (32)

PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques

Science Immunology (2021)

Keith D. Kauffman Shunsuke Sakai Nickiana E. Lora Sivaranjani Namasivayam Paul J. Baker

Blockade of the PD-1 coinhibitory pathway compromises immune control of Mycobacterium tuberculosis infection in rhesus macaques.

Rhesus macaque

10.1126/sciimmunol.abf3861

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Citations (101)