Plasma interferon-γ-inducible protein 10 (IP-10) levels correlate with disease severity and paradoxical reactions in extrapulmonary tuberculosis

Isabelle Suárez; Samuel Rohr; Melanie Stecher; Clara Lehmann; Sandra Winter; Norma Jung; Vanessa Priesner; Melanie Berger; Christoph Wyen; Max Augustin; Jakob J Malin; Julia Fischer; Carola Horn; Florian Neuhann; Michael Püsken; Georg Plum; Gerd Fätkenheuer; Jan Rybniker

doi:10.1007/s15010-020-01541-1

Plasma interferon-γ-inducible protein 10 (IP-10) levels correlate with disease severity and paradoxical reactions in extrapulmonary tuberculosis

Infection. 2021 Jun;49(3):437-445. doi: 10.1007/s15010-020-01541-1. Epub 2020 Nov 2.

Authors

Isabelle Suárez^{1

2}, Samuel Rohr¹, Melanie Stecher^{1

2}, Clara Lehmann^{1

2

3}, Sandra Winter^{1

3}, Norma Jung^{1

2}, Vanessa Priesner^{1

2}, Melanie Berger⁴, Christoph Wyen^{1

5}, Max Augustin^{1

3}, Jakob J Malin^{1

2

3}, Julia Fischer^{1

2

3}, Carola Horn^{1

3}, Florian Neuhann^{6

7

8}, Michael Püsken⁹, Georg Plum¹⁰, Gerd Fätkenheuer^{1

2}, Jan Rybniker^{11

12

13}

Affiliations

¹ Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
² German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
³ Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
⁴ Department of Pneumology and Critical Care Medicine, Cologne-Merheim Hospital, Kliniken Der Stadt Köln GmbH, Witten/Herdecke University Hospital, Ostmerheimer Strasse 200, 51109, Cologne, Germany.
⁵ Praxis Am Ebertplatz, Cologne, Germany.
⁶ Levy Mwanawasa Medical University (LMMU), Lusaka, Zambia.
⁷ Institute of Global Health, University Hospital Heidelberg, Heidelberg, Germany.
⁸ Municipal Health Authority Cologne, Cologne, Germany.
⁹ Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne, Cologne, Germany.
¹⁰ Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany.
¹¹ Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. jan.rybniker@uk-koeln.de.
¹² German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany. jan.rybniker@uk-koeln.de.
¹³ Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany. jan.rybniker@uk-koeln.de.

Abstract

Background: With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers.

Methods: The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON^®-TB Gold Plus (QFT^® Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT^® Plus and IP-10 levels.

Results: Plasma IP-10 levels were found to be significantly increased (p < 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT^® Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for Mycobacterium tuberculosis.

Conclusion: Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT^® Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.

Keywords: Biomarker; EPTB; Extrapulmonary tuberculosis; IP-10; Paradoxical reaction; QuantiFERON®-TB gold plus test.

MeSH terms

Chemokine CXCL10 / blood*
Humans
Interferon-gamma Release Tests
Mycobacterium tuberculosis
Severity of Illness Index
Tuberculosis, Lymph Node* / diagnosis

Substances

CXCL10 protein, human
Chemokine CXCL10

Abstract

MeSH terms

Substances

Grants and funding