It has been speculated that human leukocyte antigen (HLA) alleles are associated with the outcome of hepatitis B virus (HBV) infection although the data obtained from various populations have shown some inconsistencies. A total of 464 HBVinfected Korean individuals (80 spontaneously recovered [SR] and 384 chronically infected [CI]) were selected to investigate the association of HLA class II alleles with the viral clearance and persistence. Our results showed that: 1) multiple HLA class II alleles and haplotypes were associated with viral clearance (DRB1*1302, DRB1*1502, DQB1*0302, DQB1*0609, and related-haplotypes) and persistence (DRB1*0701, DQB1*0301, and related-haplotypes); 2) DRB1*1302 and DQB1* 0609 were more strongly associated with viral clearance. And the association of DQB1*0609 (pc=0.0084; OR, 7.24) with vial clearance was much stronger than previously recognized, DRB1*1302 (pc=0.0038; OR, 4.34); and 3) linkage to a specific DPB1 allele in a haplotype strengthened the association with viral clearance, although DPB1 itself was not associated with the outcome. These results indicate the existence of multiple factors controlling viral clearance in the HLA class II gene region. Further extended investigation on the genetic factors related to the outcome of HBV infection will provide valuable insights into the understanding of the mechanisms involved.
Alleles ; *Genes, MHC Class II ; HLA Antigens/*genetics ; HLA-DQ Antigens/*genetics ; HLA-DR Antigens/*genetics ; *Haplotypes ; Hepatitis B/*immunology/*virology ; Hepatitis B virus/genetics ; Humans ; Immunophenotyping ; Korea ; Models, Genetic ; Remission Induction ; Treatment Outcome

We examined the effect of class II transactivator (CIITA) down-modulation on allograft rejection. To inhibit the function of CIITA, we constructed a series of CIITA mutants and found one exhibiting the dominant-negative effect on the regulation of major histocompatibility complex (MHC) class II expression. To test whether the CIITA dominant-negative mutant reduces immunogenecity, CIITA-transfected melanoma cells were injected into allogeneic host and assessed for immune evading activity against host immune cells. We demonstrated that the CIITA dominant-negative mutant allowed tumor nodules to develop earlier in the lung than control by this tumor challenge study. Furthermore, skin grafts deficient for CIITA also survived longer than wild-type in allogeneic hosts. Both the tumor challenge and skin graft studies suggest the inhibition of CIITA molecules in donor tissue would be beneficial to the control of allo-response.
Transplantation, Homologous ; Transfection ; Trans-Activators/genetics/*immunology/metabolism ; Trans-Activation (Genetics)/genetics/immunology ; Skin Transplantation ; Nuclear Proteins/genetics/*immunology/metabolism ; Mutation ; Mice, Transgenic ; Mice, Knockout ; Mice, Inbred C57BL ; Mice, Inbred BALB C ; Mice ; Melanoma, Experimental/genetics/immunology/pathology ; Male ; Interferon Type II/pharmacology ; Humans ; Histocompatibility Antigens Class II/genetics/*immunology/metabolism ; Graft Survival/genetics/immunology ; Graft Rejection/genetics/*immunology ; Genes, MHC Class II/genetics/immunology ; Flow Cytometry ; DNA, Complementary/genetics ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Animals

Moyamoya disease is characterized by progressive cerebrovascular occlusion at the peripheral internal carotid artery and development of abnormal collateral circulation at the cerebral basal region. Although abnormal thrombogenesis, inflammation and autoimmune process might be involved in the etiology, the genetic pathogenesis of Moyamoya disease is still unknown. To evaluate the association of Moyamoya disease with HLA alleles in the Korean population, we investigated HLA class I and class II alleles in 28 Moyamoya patients and 198 unrelated healthy controls. The frequency of HLA-B35 allele was significantly increased in the patients compared to the controls (32.1% vs. 10.1%, RR=4.2, p<0.008). Further analysis of HLA-B35 on onset age and sex showed that this allele was significantly increased compared to the controls in both late-onset and female group. Especially, HLA-B35 was the most significantly increased in female of late-onset group compared to the controls. These results suggest that HLA-B35 may be an useful genetic marker for Moyamoya disease, and particularly in females of late onset group in the Korean population.
Adolescent ; Adult ; Age of Onset ; Aged ; Child ; Child, Preschool ; Female ; Gene Frequency ; *Genes, MHC Class I ; *Genes, MHC Class II ; Genetic Markers ; Genetic Predisposition to Disease ; Genotype ; HLA Antigens/*genetics ; Human ; Korea ; Male ; Middle Aged ; Moyamoya Disease/*genetics/*immunology ; Retrospective Studies ; Support, Non-U.S. Gov't