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Front Immunol. 2018 Oct 23;9:2427. doi: 10.3389/fimmu.2018.02427. eCollection 2018.

Complement Component C1q as Serum Biomarker to Detect Active Tuberculosis.

Author information

1
Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
2
Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, Gambia.
3
Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy.
4
Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
5
Department of Pulmonology, St. Antonius Hospital Nieuwegein, Nieuwegein, Netherlands.
6
Department of Internal Medicine, St. Antonius Hospital Nieuwegein, Nieuwegein, Netherlands.
7
Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands.
8
Pathology Service, National Institute for Infectious Diseases, Rome, Italy.
9
Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
10
Section of TB Research & Immunology, Biomedical Primate Research Centre, Rijswijk, Netherlands.
11
Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
12
Sanquin Diagnostic Services, Amsterdam, Netherlands.
13
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.

Abstract

Background: Tuberculosis (TB) remains a major threat to global health. Currently, diagnosis of active TB is hampered by the lack of specific biomarkers that discriminate active TB disease from other (lung) diseases or latent TB infection (LTBI). Integrated human gene expression results have shown that genes encoding complement components, in particular different C1q chains, were expressed at higher levels in active TB compared to LTBI. Methods: C1q protein levels were determined using ELISA in sera from patients, from geographically distinct populations, with active TB, LTBI as well as disease controls. Results: Serum levels of C1q were increased in active TB compared to LTBI in four independent cohorts with an AUC of 0.77 [0.70; 0.83]. After 6 months of TB treatment, levels of C1q were similar to those of endemic controls, indicating an association with disease rather than individual genetic predisposition. Importantly, C1q levels in sera of TB patients were significantly higher as compared to patients with sarcoidosis or pneumonia, clinically important differential diagnoses. Moreover, exposure to other mycobacteria, such as Mycobacterium leprae (leprosy patients) or BCG (vaccinees) did not result in elevated levels of serum C1q. In agreement with the human data, in non-human primates challenged with Mycobacterium tuberculosis, increased serum C1q levels were detected in animals that developed progressive disease, not in those that controlled the infection. Conclusions: In summary, C1q levels are elevated in patients with active TB compared to LTBI in four independent cohorts. Furthermore, C1q levels from patients with TB were also elevated compared to patients with sarcoidosis, leprosy and pneumonia. Additionally, also in NHP we observed increased C1q levels in animals with active progressive TB, both in serum and in broncho-alveolar lavage. Therefore, we propose that the addition of C1q to current biomarker panels may provide added value in the diagnosis of active TB.

KEYWORDS:

C1q; blood; complement; infection; innate immunity; mycobacterium; tuberculosis

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