Increased levels of BAFF and APRIL related to human active pulmonary tuberculosis.
BACKGROUND
Despite great efforts to improve diagnosis and treatment, tuberculosis (TB) remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant.


METHODS
To understand the nature of CD4(+) T cell-derived signatures involved in infection and disease development, we examined and analyzed whole genome expression profiles of purified CD4(+) T cells from healthy individuals (HD), two distinct populations with latent infection (with low or high IFN-γ levels, LTB(L)/LTB(H)) and untreated TB patients. Following, we validated the expression profiles of genes in the peripheral CD4(+) T cells from each group and examined secretion levels of distinct cytokines in serum and pleural effusion.


RESULTS
Our bio-informatic analyses indicate that the two latent populations and clinical TB patients possess distinct CD4(+) T cell gene expression profiles. Furthermore, The mRNA and protein expression levels of B cell activating factor (BAFF), which belongs to the TNF family, and a proliferation-inducing ligand (APRIL) were markedly up-regulated at the disease stage. In particular, the dramatic enhancement of BAFF and APRIL in the pleural effusion of patients with tuberculosis pleurisy suggests that these proteins may present disease status. In addition, we found that the BAFF/APRIL system was closely related to the Th1 immune response. Our study delineates previously unreported roles of BAFF and APRIL in the development of tuberculosis, and these findings have implications for the diagnosis of the disease. Our study also identifies a number of transcriptional signatures in CD4(+) T cells that have the potential to be utilized as diagnostic and prognostic tools to combat the tuberculosis epidemic.
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
Kai
K
Liu
Yan
Y
Zhang
Shizong
S
Hu
Yang
Y
Yu
Qianting
Q
Yang
Dongdong
D
Jin
Xinchun
X
Chen
Qi
Q
Jin
Haiying
H
Liu
D000293:Adolescent; D000328:Adult; D053264:B-Cell Activating Factor / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014397:Tuberculosis, Pulmonary / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*; D055815:Young Adult
D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13