title: Plasma levels of Galectin-9 reflect disease severity in malaria infection.
abstract: Galectin-9 (Gal-9) is a β-galactoside-binding lectin that interacts with sugar moieties on glycoproteins and glycolipids of cells and pathogens. Gal-9 is known as an immune modulator that induces cell death via interaction with T cell immunoglobulin and mucin domain-3 (Tim3), a co-inhibitory receptor, and it inhibits production of several pro-inflammatory cytokines (TNF, IL-6 and IL-1α) and enhances production of IL-10. To understand the immune pathology of malaria, the Gal-9 in plasma was measured.
  
  
  
  Plasma samples and clinical parameters were obtained from 50 acute malaria cases (nine severe and 41 uncomplicated cases) from Thailand at three time points: day 0, day 7 and day 28. Gal-9 levels were determined by ELISA. A total of 38 species of cytokines and chemokines were measured using a BioPlex assay.
  
  
  
  Gal-9 levels were higher at day 0 compared to day 7 and day 28 (P < 0.0001). Gal-9 levels were also higher in severe malaria (SM) cases compared to uncomplicated (UM) cases at day 0 and day 7 (923 vs 617 pg/mL; P = 0.03, and 659 vs 348 pg/mL; P = 0.02 respectively). Median Gal-9 levels were higher in patients with blood urea nitrogen to creatinine ratio (BUN/creatinine) ≥20 (mg/dL) than in patients with BUN/creatinine <20 (mg/dL) at day 0 (817.3 vs 576.2 pg/mL, P = 0.007). Gal-9 was inversely significantly correlated with chloride levels in both SM and UM cases (r s = -0.73 and r s = -0.46, respectively). In both UM and SM cases, Gal-9 was significantly associated with pro- and anti-inflammatory cytokines and chemokines such as TNF, IL-6, IFN-α2, IFN-γ, IL-1Ra and IL-10. These correlations were observed at day 0 but disappeared at day 28.
  
  
  
  Gal-9 is released during acute malaria, and reflects its severity. This elevation of Gal-9 in acute malaria infection raises the possibility of its role in termination of the immune response by binding to Tim-3, a receptor of Gal-9.
authors: Division of International Cooperation for Disaster Medicine, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Bindongo P P
authors: BP
authors: Dembele
authors: Division of Disaster-related Infectious Disease, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.|Emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors: Haorile
authors: H
authors: Chagan-Yasutan
authors: Department of Immunology, Kagawa University, Takamatsu, Japan.|GalPharma Co., Ltd., Takamatsu, Japan.
authors: Toshiro
authors: T
authors: Niki
authors: Division of Disaster-related Infectious Disease, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.|Emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors: Yugo
authors: Y
authors: Ashino
authors: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Noppadon
authors: N
authors: Tangpukdee
authors: Division of International Cooperation for Disaster Medicine, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
authors: Egawa
authors: E
authors: Shinichi
authors: Clinical Malaria Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors: Srivicha
authors: S
authors: Krudsood
authors: Department of Tropical Medicine and Malaria, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors: Shigeyuki
authors: S
authors: Kano
authors: Division of Disaster-related Infectious Disease, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan. hattorit@kiui.ac.jp.|Emerging Infectious Diseases, Graduate School of Medicine, Tohoku University, Sendai, Japan. hattorit@kiui.ac.jp.|Department of Occupational Therapy, Graduate School of Health Science Studies, Kibi International University, 8 Igamachi, Takahashi, Okayama, Japan. hattorit@kiui.ac.jp.
authors: Toshio
authors: T
authors: Hattori
mesh_terms: D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D037161:Galectins / Q000097:blood*; D006801:Humans; D008288:Malaria / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D013785:Thailand; D055815:Young Adult
chemical_list: D016207:Cytokines; D037161:Galectins; C105032:LGALS9 protein, human