Blood and Site of Disease Inflammatory Profiles Differ in Patients With Pericardial Tuberculosis and Human Immunodeficiency Virus Type 1

Author:

Mutavhatsindi Hygon12ORCID,Du Bruyn Elsa1ORCID,Ruzive Sheena1,Howlett Patrick1ORCID,Cerrone Maddalena134ORCID,Sher Alan5ORCID,Mayer-Barber Katrin D6ORCID,Barber Daniel L7ORCID,Ntsekhe Mpiko189ORCID,Wilkinson Robert J13489ORCID,Riou Catherine12ORCID

Affiliation:

1. Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town , Observatory , South Africa

2. Division of Medical Virology, Department of Pathology, University of Cape Town , Observatory , South Africa

3. Department of Infectious Diseases, Imperial College London , London , United Kingdom

4. The Francis Crick Institute , London , United Kingdom

5. Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA

6. Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA

7. T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA

8. Department of Medicine, University of Cape Town , Observatory , South Africa

9. Division of Cardiology, Department of Medicine, University of Cape Town , Observatory , South Africa

Abstract

AbstractBackgroundTo better understand the pathogenesis of pericardial tuberculosis (PCTB), we sought to characterize the systemic inflammatory profile in people with human immunodeficiency virus type 1 (HIV-1) with latent TB infection (LTBI), pulmonary TB (PTB), or PCTB.MethodsUsing Luminex, we measured the concentration of 39 analytes in pericardial fluid (PCF) and paired plasma from 18 PCTB participants, and plasma from 16 LTBI and 20 PTB participants. Follow-up plasma samples were also obtained from PTB and PCTB participants. HLA-DR expression on Mycobacterium tuberculosis–specific CD4 T cells was measured in baseline samples using flow cytometry.ResultsAssessment of the overall systemic inflammatory profile by principal component analysis showed that the inflammatory profile of active TB participants was distinct from the LTBI group, while PTB patients could not be distinguished from those with PCTB. When comparing the inflammatory profile between PCF and paired blood, we found that the concentrations of most analytes (25/39) were elevated at site of disease. However, the inflammatory profile in PCF partially mirrored inflammatory events in the blood. After TB treatment completion, the overall plasma inflammatory profile reverted to that observed in the LTBI group. Lastly, HLA-DR expression showed the best performance for TB diagnosis compared to previously described biosignatures built from soluble markers.ConclusionsOur results show that the inflammatory profile in blood was comparable between PTB and PCTB. However, at the site of infection (PCF), inflammation was significantly elevated compared to blood. Additionally, our data emphasize the potential role of HLA-DR expression as a biomarker for TB diagnosis.

Funder

European and Developing Countries Clinical Trials Partnership

European Union

Horizon 2020

National Institutes of Health

South African Medical Research Council

Francis Crick Institute

Cancer Research UK

Wellcome

UK Medical Research Council

National Research Foundation of South Africa

CIDRI-Africa Fellowship,

Fogarty International Center, NIH

Division of Intramural Research,

National Institute of Allergy and Infectious Diseases

NIH

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

Reference51 articles.

1. Extrapulmonary tuberculosis;Sharma;Indian J Med Res,2004

2. Extrapulmonary tuberculosis in immunocompetent adults;Cagatay;Scand J Infect Dis,2004

3. Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection;Shafer;Medicine (Baltimore),1991

4. Extrapulmonary tuberculosis in the United States;Rieder;Am Rev Respir Dis,1990

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