Size and charge characteristics of the protein leak in dengue shock syndrome.
BACKGROUND
he mechanism underlying the transient vascular leak syndrome of dengue hemorrhagic fever (DHF) is unknown. We aimed to determine whether molecular size and charge selectivity, which help restrict plasma proteins within the intravascular space, are altered in patients with DHF and whether a disturbance of the anionic glycosaminoglycan (GAG) layer on the luminal endothelial surface contributes to disease pathogenesis.


METHODS
We measured serial plasma levels and fractional clearances of proteins with different size and charge characteristics in 48 children with dengue shock syndrome (DSS) and urinary excretion profiles of heparan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate in affected children and healthy control subjects.


RESULTS
Compared with convalescent values, acute plasma concentrations of all proteins were reduced, with increased fractional clearances. Smaller proteins were more affected than larger molecules. Albumin, which is normally protected from leakage by its strong negative charge, demonstrated a clearance pattern similar to that of transferrin, a neutral molecule of similar size. Urinary heparan sulfate excretion was significantly increased in children with DSS.


CONCLUSIONS
The endothelial size-dependent sieving mechanism for plasma proteins is at least partially retained, whereas selective restriction based on negative charge is impaired. The increased heparan sulfate excretion suggests a role for GAGs in the pathogenesis of the vascular leak.
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. bridgetw@hcm.vnn.vn.
Bridget A
BA
Wills
Emmanuelle E
EE
Oragui
Nguyen Minh
NM
Dung
Ha Thi
HT
Loan
Nguyen Vinh
NV
Chau
Jeremy J
JJ
Farrar
Michael
M
Levin
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000097:blood / Q000652:urine; D003716:Dengue Virus; D005260:Female; D006497:Heparan Sulfate / Q000652:urine; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D012709:Serum Albumin / Q000032:analysis; D019595:Severe Dengue / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013997:Time Factors; D014168:Transferrin / Q000032:analysis
D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D007074:Immunoglobulin G; D012709:Serum Albumin; D014168:Transferrin