TY - JOUR
T1 - Inverse correlation between serum complement component C1q levels and whole blood type-1 interferon signature in active tuberculosis and QuantiFERON-positive uveitis
T2 - implications for diagnosis
AU - Schrijver, Benjamin
AU - Dijkstra, Douwe J.
AU - Borggreven, Nicole V.
AU - La Distia Nora, Rina
AU - Huijser, Erika
AU - Versnel, Marjan A.
AU - van Hagen, P. Martin
AU - Joosten, Simone A.
AU - Trouw, Leendert A.
AU - Dik, Willem A.
N1 - Funding Information:
We are grateful to all participants who donated blood for these studies. We acknowledge the efforts of Professor Drs R Sitompul, M Susiyanti, L Edwar, S Sjamsoe (Department of Internal Medicine, Respirology and Critical Illness Division, University of Indonesia & Cipto Mangunkusumo Hospital Kirana, Jakarta, Indonesia), Dr G Singh (Department of Internal Medicine, Respirology and Critical Illness Division, University of Indonesia & Cipto Mangunkusumo Hospital Kirana, Jakarta, Indonesia) and Dr RR Diah Handayani (Department of Pulmonology, Persahabatan Hospital, Jakarta, Indonesia) for patient inclusion and sample collection of cohort 1. We also acknowledge Dr B Alisjahbana (Department of Internal Medicine, Hasan Sadikin General Hospital, Bandung, Indonesia, & Infectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia) and his team for patient inclusion and sample collection of cohort 2.
Publisher Copyright:
© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - Objectives: To examine the relation between serum C1q levels and blood type-1 interferon signature (type-1 IFN signature) in active pulmonary tuberculosis (APTB) and to determine whether combined measurement of serum C1q and type-1 IFN signature may add to the diagnosis of QuantiFERON-positive (QFT+) patients with uveitis of unknown cause. Methods: C1q was determined (ELISA) in serum from two distinct Indonesian cohorts, and in total, APTB (n = 72), QFT+ uveitis of unknown aetiology (n = 58), QFT− uveitis (n = 51) patients and healthy controls (HC; n = 73) were included. The type-1 IFN signature scores were previously determined. Results: Serum C1q was higher in APTB than HC (P < 0.001). APTB patients with uveitis had higher serum C1q than APTB patients without uveitis (P = 0.0207). Serum C1q correlated inversely with type-1 IFN signature scores in APTB (P = 0.0036, r2 = 0.3526), revealing that these biomarkers for active TB disease can be mutually exclusive. Stratification of QFT+ patients with uveitis of unknown cause, by serum C1q and type-1 IFN signature, yielded four groups with different likelihood of suffering from active TB uveitis. Conclusion: Serum C1q is elevated in APTB, especially in those cases with uveitis. We propose that combined measurement of blood type-1 IFN signature and serum C1q may provide added value in the diagnosis of active TB disease. Combined measurement of type-1 IFN signature and serum C1q in QFT+ patients without signs of active TB disease, but suffering from uveitis of unknown cause, may be of help to identify cases with low or high likelihood of having active TB uveitis, which may facilitate clinical management decisions.
AB - Objectives: To examine the relation between serum C1q levels and blood type-1 interferon signature (type-1 IFN signature) in active pulmonary tuberculosis (APTB) and to determine whether combined measurement of serum C1q and type-1 IFN signature may add to the diagnosis of QuantiFERON-positive (QFT+) patients with uveitis of unknown cause. Methods: C1q was determined (ELISA) in serum from two distinct Indonesian cohorts, and in total, APTB (n = 72), QFT+ uveitis of unknown aetiology (n = 58), QFT− uveitis (n = 51) patients and healthy controls (HC; n = 73) were included. The type-1 IFN signature scores were previously determined. Results: Serum C1q was higher in APTB than HC (P < 0.001). APTB patients with uveitis had higher serum C1q than APTB patients without uveitis (P = 0.0207). Serum C1q correlated inversely with type-1 IFN signature scores in APTB (P = 0.0036, r2 = 0.3526), revealing that these biomarkers for active TB disease can be mutually exclusive. Stratification of QFT+ patients with uveitis of unknown cause, by serum C1q and type-1 IFN signature, yielded four groups with different likelihood of suffering from active TB uveitis. Conclusion: Serum C1q is elevated in APTB, especially in those cases with uveitis. We propose that combined measurement of blood type-1 IFN signature and serum C1q may provide added value in the diagnosis of active TB disease. Combined measurement of type-1 IFN signature and serum C1q in QFT+ patients without signs of active TB disease, but suffering from uveitis of unknown cause, may be of help to identify cases with low or high likelihood of having active TB uveitis, which may facilitate clinical management decisions.
KW - C1q
KW - complement
KW - extrapulmonary tuberculosis
KW - QuantiFERON
KW - type-1 interferon signature
KW - uveitis
UR - http://www.scopus.com/inward/record.url?scp=85094147725&partnerID=8YFLogxK
U2 - 10.1002/cti2.1196
DO - 10.1002/cti2.1196
M3 - Article
AN - SCOPUS:85094147725
SN - 2050-0068
VL - 9
JO - Clinical and Translational Immunology
JF - Clinical and Translational Immunology
IS - 10
M1 - e1196
ER -