Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients
Molecular Immunology, vol. 120, pp. 187–195
Abstract
BACKGROUND: To facilitate better discrimination between patients with active tuberculosis (TB) and latent TB infection (LTBI), whole blood transcriptomic studies have been performed to identify novel candidate host biomarkers. SERPING1, which encodes C1-inhibitor (C1-INH), the natural inhibitor of the C1-complex has emerged as candidate biomarker. Here we collated and analysed SERPING1 expression data and subsequently determined C1-INH protein levels in four cohorts of patients with TB. METHODS: SERPING1 expression data were extracted from online deposited datasets. C1-INH protein levels were determined by ELISA in sera from individuals with active TB, LTBI as well as other disease controls in geographically diverse cohorts. FINDINGS: SERPING1 expression was increased in patients with active TB compared to healthy controls (8/11 cohorts), LTBI (13/14 cohorts) and patients with other (non-TB) lung-diseases (7/7 cohorts). Serum levels of C1-INH were significantly increased in The Gambia and Italy in patients with active TB relative to the endemic controls but not in South Africa or Korea. In the largest cohort (n = 50), with samples collected longitudinally, normalization of C1-INH levels following successful TB treatment was observed. This cohort, also showed the most abundant increase in C1-INH, and a positive correlation between C1q and C1-INH levels. Combined presence of increased levels of both C1q and C1-INH had high specificity for active TB (96 %) but only very modest sensitivity 38 % compared to the endemic controls. INTERPRETATION: SERPING1 transcript expression is increased in TB patients, while serum protein levels of C1-INH were increased in half of the cohorts analysed.
Authors 18
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Leiden University Medical Center
Affiliation as printed
Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands
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MRC Unit the Gambia · Medical Research Council
Affiliation as printed
Vaccines and Immunity Theme, Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia
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Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Affiliation as printed
Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases L. Spallanzani-IRCCS, Rome, Italy
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
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Affiliation as printed
Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands
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Affiliation as printed
Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands
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Affiliation as printed
Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands
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Leiden University Medical Center · St. Antonius Ziekenhuis
Affiliation as printed
Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands
Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
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Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Affiliation as printed
Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases L. Spallanzani-IRCCS, Rome, Italy
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South African Medical Research Council · Stellenbosch University
Affiliation as printed
DST/NRF Centre of Excellence for Biomedical TB Research and SAMRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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South African Medical Research Council · Stellenbosch University
Affiliation as printed
DST/NRF Centre of Excellence for Biomedical TB Research and SAMRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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Affiliation as printed
Sanquin Diagnostic Services, Amsterdam, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: L.A.Trouw@lumc.nl
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
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