Serological biomarker screening and host factor analysis elucidating immune response heterogeneity in active pulmonary tuberculosis
- Author:
Mohd Hanafiah, K.
;
Liu, J.J.
;
Lieschke, K.
;
Barnes, N.C.
;
Garcia, M.L.
;
Anderson, D.A.
- Publication Type:Original Article
- From:Tropical Biomedicine
2017;34(3):556-569
- CountryMalaysia
- Language:English
-
Abstract:
While mortality and morbidity from pulmonary tuberculosis (PTB) have improved,
diagnosis of this infectious disease remains suboptimal without a point-of-care test. Antibody/
antigen-based serodiagnostics is the most amenable for point-of-care translation but hampered
by a lack of validated biomarkers and a heterogeneous patient antibody response. Using a
case-control design, we assessed serodiagnostic potential of immunoglobulins G, A, and
dimeric IgA responses against 18 antigenic preparations, followed by antibody-subclass
responses against antigen 60 (A60), and four markers of host innate immunity by enzymelinked
immunoassay using sera samples (n=110) collected from April to October 2007 in
VietNam from human immunodeficiency-negative patients with provisional diagnosis of PTB.
We further analyzed host variables to investigate factors driving biomarker heterogeneity
observed in patients. Among active pulmonary tuberculosis patients, low correlation was
observed between anti-A60 antibody-classes, and between anti-A60 immunoglobulin G
subclasses, but anti-A60 immunoglobulin A subclasses were significantly correlated. The
best diagnostic combination of anti-A60 immunoglobulin G/A and a C-reactive protein “ruleout”
remains insufficient at 82%/92% sensitivity/specificity (95%CI: 72-92%/82-98%).
Heterogeneity of anti-A60 immunoglobulins G2, G3, M, as well as C-reactive protein and
serum amyloid A levels observed in this study population appeared to be significantly
associated with history of previous tuberculosis, hemoptysis, age, vaccination, night sweats,
smoking, chest pain, fever, alcohol, and solid culture count. Further research on tuberculosis
serological biomarkers may require consideration of host factors and new approaches using
multiple biomarkers.
