The Role of Chemokines and Chemokine Receptors in Patients with Dengue Fever versus Dengue Hemorrhagic Fever

Autor: Cho-Kuang Shen, 沈倬光
Rok vydání: 2003
Druh dokumentu: 學位論文 ; thesis
Popis: 91
ENGLISH ABSTRACT The possible role of immnopathogenesis in leading to dengue patients manifested with the severe form of dengue hemorrhagic fever (DHF) versus mild form of dengue fever (DF) caused by the same serotype of dengue virus during the same epidemic has not been fully understood. The specific aims of this study were to determine whether there are differences in the expression of two important chemokine receptors (CCR5 and CXCR3) related to virus infection or the levels of their relevant chemokines (RANTES, IP-10, Mig and MIP-1α) associated with hemorrhage or liver function or certain clinical complications in DHF versus DF patients. A prospective follow-up cohort study design was employed to recruit 23 DHF and 77 DF patients caused by dengue virus serotype 2 plus 46 healthy donors from Aug. 2, 2002 to Mar. 31, 2003 in Kaohsiung and Pingtung, Taiwan. Human whole blood samples of dengue patients and healthy controls were stained with antibodies of two chemokine receptors (CCR5 and CXCR3) or CD45RO plus CD62L to classify into naïve, central memory and effector memory subpopulations of both CD4+ T and CD8+ T cells, and then quantify those positive stained cells by flow cytometry. Levels of RANTES, IP-10, Mig, MIP-1a were also measured in serum samples collected at both the first visit and subsequent repeated visits. Mann-Whitney U test and Spearman correlation test were used to compare the relationship between above each chemokine / chemokine receptors and clinical severity of dengue or hemodynamic/biochemical laboratory findings, and their kinetic changes at different time points after the onset of fever in DHF vs DF patients, respectively. Our results found that dengue fever patients had significantly lower expression of CXCR3 in CD8 T cells (DF patients: 23.75+ 2.87 vs controls: 43.39+ 29.87, p=0.001) and significantly lower mean ratio of CD4+T/CD3+T cells than healthy controls (DF patients: 33.19+ 2.21 vs controls: 40.13 + 15.94, p=0.03). In addition, dengue patients had significantly higher serum levels of RANTES (DHF: 13.69+3.46 vs DF: 19.56+2.74, controls: 2.21+0.78 ng/ml, p 7 days after the onset of fever whereas the serum levels of RANTES in these two time intervals were reverse; (4) levels of RANTES in serum were positively correlated with higher expression of CCR5 on CD8+CD3+T cells in DHF patients (r=0.39,P=0.023) and quantities of RANTES were further significantly correlated with two most important hematological abnormalities (platelet number (p
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