Cytomegalovirus Antibody Responses Associated With Increased Risk of Tuberculosis Disease in Ugandan Adults.
Adolescent
Adult
Antibodies, Viral
/ blood
Case-Control Studies
Chemokine CXCL10
/ blood
Child
Child, Preschool
Cytomegalovirus
/ immunology
Cytomegalovirus Infections
/ complications
Female
Humans
Male
Middle Aged
Mycobacterium tuberculosis
/ immunology
Rural Population
Tuberculosis
/ complications
Uganda
Young Adult
CXCL10
Case-control
HCMV
IP-10
Uganda
cytomegalovirus
tuberculosis
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
16 03 2020
16 03 2020
Historique:
received:
12
08
2019
accepted:
04
11
2019
pubmed:
7
11
2019
medline:
5
1
2021
entrez:
6
11
2019
Statut:
ppublish
Résumé
Recent evidence highlights human cytomegalovirus (HCMV) and immune activation as risk factors for tuberculosis disease. It is not known whether other herpesviruses are also implicated, nor whether a dose-response relationship exists between tuberculosis risk and herpes coinfection. This nested case-control study used stored serum samples from 25 persons with tuberculosis up to 10 years before tuberculosis diagnosis and between 3 and 6 matched controls without tuberculosis from a rural Ugandan cohort. Samples were investigated for Epstein-Barr virus, herpes simplex virus, and HCMV-specific immunoglobulin G (IgG), serum markers of inflammation, and mycobacterial antibody levels. Humoral response to HCMV, but not Epstein-Barr or herpes simplex virus, was associated with increased risk of active tuberculosis disease up to 10 years before diagnosis. Individuals with medium HCMV IgG were 2.8 times more likely to have tuberculosis (P = .055), and those with high HCMV IgG 3.4 times more likely to have tuberculosis (P = .007). Mycobacterial antibody levels were not associated with differences in odds of tuberculosis disease. Interferon-induced protein 10 was independently associated with increased odds of tuberculosis (odds ratio, 4.2; P = .009). These data provide evidence of a dose response between magnitude of HCMV IgG with risk of tuberculosis disease. An inflammatory environment, characterized by serum interferon-induced protein 10 and interleukin 1α, is independently associated with increased risk of tuberculosis disease.
Sections du résumé
BACKGROUND
Recent evidence highlights human cytomegalovirus (HCMV) and immune activation as risk factors for tuberculosis disease. It is not known whether other herpesviruses are also implicated, nor whether a dose-response relationship exists between tuberculosis risk and herpes coinfection.
METHODS
This nested case-control study used stored serum samples from 25 persons with tuberculosis up to 10 years before tuberculosis diagnosis and between 3 and 6 matched controls without tuberculosis from a rural Ugandan cohort. Samples were investigated for Epstein-Barr virus, herpes simplex virus, and HCMV-specific immunoglobulin G (IgG), serum markers of inflammation, and mycobacterial antibody levels.
RESULTS
Humoral response to HCMV, but not Epstein-Barr or herpes simplex virus, was associated with increased risk of active tuberculosis disease up to 10 years before diagnosis. Individuals with medium HCMV IgG were 2.8 times more likely to have tuberculosis (P = .055), and those with high HCMV IgG 3.4 times more likely to have tuberculosis (P = .007). Mycobacterial antibody levels were not associated with differences in odds of tuberculosis disease. Interferon-induced protein 10 was independently associated with increased odds of tuberculosis (odds ratio, 4.2; P = .009).
CONCLUSIONS
These data provide evidence of a dose response between magnitude of HCMV IgG with risk of tuberculosis disease. An inflammatory environment, characterized by serum interferon-induced protein 10 and interleukin 1α, is independently associated with increased risk of tuberculosis disease.
Identifiants
pubmed: 31689350
pii: 5613526
doi: 10.1093/infdis/jiz581
doi:
Substances chimiques
Antibodies, Viral
0
CXCL10 protein, human
0
Chemokine CXCL10
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1127-1134Subventions
Organisme : Medical Research Council
ID : MC_UU_00027/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R010161/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J003999/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K012126/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.