Galectin-9 plasma levels reflect adverse hematological and immunological features in acute dengue virus infection.
BACKGROUND
Dengue virus (DENV) infection remains a major public health burden worldwide. Soluble mediators may play a critical role in the pathogenesis of acute DENV infection. Galectin-9 (Gal-9) is a soluble β-galactoside-binding lectin, with multiple immunoregulatory and inflammatory properties.


OBJECTIVE
To investigate plasma Gal-9 levels as a biomarker for DENV infection.


METHODS
We enrolled 65 DENV infected patients during the 2010 epidemic in the Philippines and measured their plasma Gal-9 and cytokine/chemokine levels, DENV genotypes, and copy number during the critical and recovery phases of illness.


RESULTS
During the critical phase, Gal-9 levels were significantly higher in DENV infected patients compared to healthy or those with non-dengue febrile illness. The highest Gal-9 levels were observed in dengue hemorrhagic fever (DHF) patients (DHF: 2464 pg/ml; dengue fever patients (DF): 1407 pg/ml; non-dengue febrile illness: 616 pg/ml; healthy: 196 pg/ml). In the recovery phase, Gal-9 levels significantly declined from peak levels in DF and DHF patients. Gal-9 levels tracked viral load, and were associated with multiple cytokines and chemokines (IL-1α, IL-8, IP-10, and VEGF), including monocyte frequencies and hematologic variables of coagulation. Further discriminant analyses showed that eotaxin, Gal-9, IFN-α2, and MCP-1 could detect 92% of DHF and 79.3% of DF, specifically (P<0.01).


CONCLUSIONS
Gal-9 appears to track DENV inflammatory responses, and therefore, it could serve as an important novel biomarker of acute DENV infection and disease severity.
Laboratory of Disaster-Related Infectious Disease, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan; Division of Emerging Infectious Diseases, Department of Internal Medicine, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Haorile
H
Chagan-Yasutan
Lishomwa C
LC
Ndhlovu
Talitha Lea
TL
Lacuesta
Toru
T
Kubo
Prisca Susan A
PS
Leano
Toshiro
T
Niki
Shigeru
S
Oguma
Kouichi
K
Morita
Glen M
GM
Chew
Jason D
JD
Barbour
Elizabeth Freda O
EF
Telan
Mitsuomi
M
Hirashima
Toshio
T
Hattori
Efren M
EM
Dimaano
D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D003715:Dengue / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D058872:Epidemics; D037161:Galectins / Q000097:blood*; D006801:Humans; D010679:Philippines / Q000453:epidemiology; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; D037161:Galectins; C105032:LGALS9 protein, human
Biomarker; Dengue fever; Dengue hemorrhagic fever; Dengue virus; Galectin-9