title: Cytotoxic factor-autoantibodies: possible role in the pathogenesis of dengue haemorrhagic fever.
abstract: During dengue virus infection a unique cytokine, cytotoxic factor (hCF), is produced that is pathogenesis-related and plays a key role in the development of dengue haemorrhagic fever (DHF). However, what regulates the adverse effects of hCF is not known. We have previously shown that anti-hCF antibodies raised in mice, neutralise the pathogenic effects of hCF. In this study we have investigated the presence and levels of hCF-autoantibodies in sera of patients with various severity of dengue illness (n=136) and normal healthy controls (n=50). The highest levels of hCF-autoantibodies (mean+/-S.D.=36+/-20 U ml(-1)) were seen in patients with mild illness, the dengue fever (DF), and 48 out of 50 (96%) of the sera were positive. On the other hand the hCF-autoantibody levels declined sharply with the development of DHF and the levels were lowest in patients with DHF grade IV (mean+/-S.D.=5+/-2 U ml(-1); P=<0.001 as compared to DF). Only one of the 13 DHF grade IV patients had an antibody level above the 'cut-off' value (mean plus 3 S.D. of the control sera). The analysis of data with respect to different days of illness further showed that the highest levels of hCF-autoantibodies were present in DF patients at >9 days of illness. Moreover, the DF patients at all time points, i.e. 1-4, 5-8 and >9 days of illness had significantly higher levels of hCF-autoantibodies (P<0.001) than patients with DHF grade I, II, III and IV. In addition DHF grade I and grade II patients had significantly more positive specimens than DHF grade III and grade IV patients at all time points. These results suggest that elevated levels of hCF-autoantibodies protect the patients against the development of severe forms of DHF and, therefore, it may be useful as a prognostic indicator.
authors.affiliation: Department of Microbiology, Faculty of medicine, Kuwait University, P.O Box 24923, 13110 Safat, Kuwait.
authors.forename: U C
authors.initials: UC
authors.lastname: Chaturvedi
authors.forename: E A
authors.initials: EA
authors.lastname: Elbishbishi
authors.forename: R
authors.initials: R
authors.lastname: Agarwal
authors.forename: A S
authors.initials: AS
authors.lastname: Mustafa
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D016207:Cytokines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D006801:Humans; D011379:Prognosis; D019595:Severe Dengue / Q000097:blood / Q000821:virology*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; C087354:dengue-2 virus-induced cytotoxic factor