Protective and Enhancing HLA Alleles, HLA-DRB1*0901 and HLA-A*24, for Severe Forms of Dengue Virus Infection, Dengue Hemorrhagic Fever and Dengue Shock Syndrome

Dengue has become one of the most common viral diseases transmitted by infected mosquitoes (with any of the four dengue virus serotypes: DEN-1, -2, -3, or -4). It may present as asymptomatic or illness, ranging from mild to severe disease. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. The pathogenesis of DHF/DSS, however, is not yet completely understood. The immune response, virus virulence, and host genetic background are considered to be risk factors contributing to disease severity. Human leucocyte antigens (HLA) expressed on the cell surface function as antigen presenting molecules and those polymorphism can change individuals' immune response. We investigated the HLA-A, -B (class I), and -DRB1 (class II) polymorphism in Vietnamese children with different severity (DHF/DSS) by a hospital-based case-control study. The study showed persons carrying HLA-A*2402/03/10 are about 2 times more likely to have severe dengue infection than others. On the other hand, HLA-DRB1*0901 persons are less likely to develop DSS with DEN-2 virus infection. These results clearly demonstrated that HLA controlled the susceptibility to severe forms of DV infection