Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients

dc.contributor.authorLubbers, Rosalieen_ZA
dc.contributor.authorSutherland, Jayne S.en_ZA
dc.contributor.authorGoletti, Deliaen_ZA
dc.contributor.authorDe Paus, Roelof A.en_ZA
dc.contributor.authorDijkstra, Douwe J.en_ZA
dc.contributor.authorVan Moorsel, Coline H. M.en_ZA
dc.contributor.authorVeltkamp, Marcelen_ZA
dc.contributor.authorVestjens, Stefan M. T.en_ZA
dc.contributor.authorBos, Willem J. W.en_ZA
dc.contributor.authorPetrone, Lindaen_ZA
dc.contributor.authorMalherbe, Stephanus T.en_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorGelderman, Kyra A.en_ZA
dc.contributor.authorGroeneveld, Geert H.en_ZA
dc.contributor.authorGeluk, Annemiekeen_ZA
dc.contributor.authorOttenhoff, Tom H. M.en_ZA
dc.contributor.authorJoosten, Simone A.en_ZA
dc.contributor.authorTrouw, Leendert A.en_ZA
dc.date.accessioned2023-01-20T07:05:41Zen_ZA
dc.date.available2023-01-20T07:05:41Zen_ZA
dc.date.issued2020-03-13en_ZA
dc.descriptionCITATION: Lubbers, R. et al. 2020. Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients. Molecular Immunology, 120:187–195, doi:10.1016/j.molimm.2020.02.006.en_ZA
dc.descriptionThe original publication is available at https://www.sciencedirect.comen_ZA
dc.description.abstractBackground 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.en_ZA
dc.description.versionPublisher's versionen_ZA
dc.format.extent9 pagesen_ZA
dc.identifier.citationLubbers, R. et al. 2020. Expression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patients. Molecular Immunology, 120:187–195, doi:10.1016/j.molimm.2020.02.006.en_ZA
dc.identifier.issn1872-9142 (online)en_ZA
dc.identifier.issn0161-5890 (print)en_ZA
dc.identifier.otherdoi:10.1016/j.molimm.2020.02.006en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/126265en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherElsevieren_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis -- Patientsen_ZA
dc.subjectSerine proteinases -- Inhibitorsen_ZA
dc.subjectBiochemical markersen_ZA
dc.subjectLatent virus diseasesen_ZA
dc.subjectNatural immunityen_ZA
dc.titleExpression and production of the SERPING1-encoded endogenous complement regulator C1-inhibitor in multiple cohorts of tuberculosis patientsen_ZA
dc.typeArticleen_ZA
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