title: Circulating granulysin levels in healthcare workers and latent tuberculosis infection estimated using interferon-gamma release assays.
abstract: Granulysin (GNLY) is produced by human lymphocyte subpopulations and exhibits antimicrobial activity against Mycobacterium tuberculosis. We examined the association between GNLY levels in blood and latent tuberculosis (TB) infection.
  
  
  
  Latency of TB infection among Vietnamese healthcare workers was estimated using interferon-gamma release assays (IGRA), and serum GNLY concentrations were measured using enzyme-linked immunosorbent assays. The levels of GNLY expression in whole blood and the presence of GNLY alleles with the exon-4 polymorphism rs11127 were also determined using PCR-based methods.
  
  
  
  Among 109 study participants, 41 (37.6 %) were IGRA positive and had significantly lower serum GNLY concentrations compared with IGRA-negative participants (adjusted mean, 95 % confidence interval; 2.03, 1.72-2.44 vs. 2.48, 2.10-2.92 ng/ml, P = 0.0127; analysis of covariance). Serum GNLY concentrations and TB antigen-stimulated interferon-gamma values were weakly inversely correlated (r = -0.20, P = 0.0333). Serum GNLY concentrations varied with GNLY genotypes even after adjustment for gender and age (adjusted P = 0.0015) and were moderately correlated with GNLY expression in blood cells (r = 0.40, P < 0.0001). In subsequent analyses, low serum GNLY concentrations were significantly associated with IGRA status (adjusted odds ratio and 95 % confidence interval, 0.55 and 0.31-0.98, respectively), although GNLY genotype and mRNA levels were not.
  
  
  
  Decreased GNLY, presumably at the protein level, is linked to the immunological condition of latent TB infection.
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam. phamhuuthuong.hth@gmail.com.
authors.forename: Pham Huu
authors.initials: PH
authors.lastname: Thuong
authors.affiliation: Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Do Bang
authors.initials: DB
authors.lastname: Tam
authors.affiliation: Bureau of International Medical Cooperation, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Sakurada
authors.affiliation: NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam.
authors.forename: Nguyen Thi Le
authors.initials: NT
authors.lastname: Hang
authors.affiliation: Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis JATA, Tokyo, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Hijikata
authors.affiliation: Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Le Thi
authors.initials: LT
authors.lastname: Hong
authors.affiliation: NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam.
authors.forename: Phan Thi Minh
authors.initials: PT
authors.lastname: Ngoc
authors.affiliation: Department of National Tuberculosis Program, Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Pham Thu
authors.initials: PT
authors.lastname: Anh
authors.affiliation: Hanoi Department of Health, Hanoi, Vietnam.
authors.forename: Vu Cao
authors.initials: VC
authors.lastname: Cuong
authors.affiliation: Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis JATA, Tokyo, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsushita
authors.affiliation: Hanoi Department of Health, Hanoi, Vietnam.
authors.forename: Luu Thi
authors.initials: LT
authors.lastname: Lien
authors.affiliation: Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis JATA, Tokyo, Japan.|National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Keicho
mesh_terms: D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006282:Health Personnel; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D059425:Interferon-gamma Release Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis*; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; C075005:GNLY protein, human; D007371:Interferon-gamma
keywords: Biomarker; Gene expression; Genotype; Granulysin; Latent tuberculosis infection; Serum concentration