Molecular characterization of swine leukocyte antigen (SLA) genes is important for elucidating the immune responses between swine-donor and human-recipient in xenotransplantation. Examination of associations between alleles of SLA class I genes, type of pig genetic modification, porcine endogenous retrovirus (PERV) viral titer, and PERV subtypes may shed light on the nature of xenograft acceptance or rejection and the safety of xenotransplantation. No significant difference in PERV gag RNA level between transgenic and non-transgenic pigs was noted; likewise, the type of applied transgene had no impact on PERV viremia. SLA-1 gene profile type may correspond with PERV level in blood and thereby influence infectiveness. Screening of pigs should provide selection of animals with low PERV expression and exclusion of specimens with PERV-C in the genome due to possible recombination between A and C subtypes, which may lead to autoinfection. Presence of PERV-C integrated in the genome was detected in 31.25% of specimens, but statistically significant increased viremia in specimens with PERV-C was not observed. There is a need for multidirectional molecular characterization (SLA typing, viremia estimation, and PERV subtype screening) of animals intended for xenotransplantation research in the interest of xeno-recipient safety.
Alleles ; Animals ; Endogenous Retroviruses ; Genes, MHC Class I ; Genes, MHC Class II ; Genome ; Heterografts ; Leukocytes ; Mass Screening ; Recombination, Genetic ; Retroviridae ; RNA ; Swine ; Transgenes ; Transplantation, Heterologous ; Viremia

OBJECTIVETo investigate the frequencies of HLA-Alu repeat polymorphisms (AluMICB, AluTF, AluHJ, AluHG and AluHF) in Chinese Lisu and Nu ethnic populations.

METHODSThe frequencies of HLA-Alu repeat polymorphisms in above populations were determined with polymerase chain reaction (PCR). The associations between HLA-Alu repeat polymorphisms and HLA-A, HLA-B and HLA-C alleles were also analyzed. Phylogenetic trees were constructed with genetic distance calculated from the frequencies of HLA-Alu repeat polymorphisms.

RESULTSFrequencies of AluTF*2 and AluHF*2 were different between the two populations (P< 0.05), while those of other three insertions were similar. The strength of association between HLA-Alus and HLA alleles were different (P< 0.05) in the two populations. Although AluMICB*2 were associated with HLA-B*56:01 in both populations, the association was stronger in Lisu population (74.0%) but moderate in Nu population (30.7%). HLA-Alus were associated with particular HLA subtypes, e.g., AluHG*2 with certain HLA-A*02 subtypes. By phylogenetic analysis, Lisu and Nu were clustered together with southern Chinese and Thai populations.

CONCLUSIONThe distribution of HLA-Alus and the strength of associations between HLA-Alus and HLA class I alleles have varied between the two populations. Study of this association may facilitate identification of origins, evolution, progenitor haplotypes and recombination within the HLA class I region.

Adolescent ; Adult ; Aged ; Alleles ; Alu Elements ; Asian Continental Ancestry Group ; genetics ; Child ; Female ; Genes, MHC Class I ; Humans ; Male ; Middle Aged ; Phylogeny ; Polymorphism, Genetic ; Young Adult

Astragalus Plant ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Genes, MHC Class I ; genetics ; HL-60 Cells ; Humans ; K562 Cells ; Killer Cells, Natural ; drug effects ; Leukemia ; genetics ; metabolism ; Polysaccharides ; pharmacology

To study the allele frequencies and their polymorphism characteristics of human platelet antigen (HPA) and human leucocyte antigen-I (HLA-I) in Chinese xi'an population, the types of HPA and HLA-I in 375 Chinese xi'an voluntary platelet donors were detected by PCR-SSP and PCR-SSO as well as flow cytometry with magnetic beads, and were analyzed. The results showed that there was no polymorphism in HPA-7-HPA-14, HPA-16 and HPA-17 which only expressed-aa type, the -bb type was only detected in HPA-3 and HPA-15, 9 out of 16 samples for the HPA-5ab phenotype simultaneously expressed HPA-15ab, the other 7 samples expressed HPA-15bb, no HPA-15aa phenotype was observed. Phenotypes detected in this study were HPA-1aa-17aa, HPA-1ab, -2ab, -3ab, -3bb, -4ab, -5ab, -6ab, -15ab and -15bb. Among 375 cases, HLA-A specificity of 16 species was observed, which accounted for 76% (16/21) of detectable phenotype specificity in this locus, moreover, 11 species showed frequency > 1%; HLA-B specificity of 36 species was observed which accounted for 84% (36/43) of detectable phenotype specificity in this locus, moreover 23 species showed frequency > 1%, these species were covered by common specific HLA-I in northern China, 264 species haplotype HLA-A-B were found in 375 cases, the frequency of 30 species was > 1%. It is concluded that the gene frequency distribution of HPA and HLA-I in Chinese Xi'an population is in accordance with population of northern China on the whole, but it has its own characteristics.
Adolescent ; Adult ; Alleles ; Antigens, Human Platelet ; genetics ; Asian Continental Ancestry Group ; genetics ; Blood Donors ; China ; Female ; Genes, MHC Class I ; Humans ; Male ; Middle Aged ; Phenotype ; Young Adult

OBJECTIVETo investigate the risk factors for sensitization of anti-MICA antibodies and their impact on the outcomes of renal transplantation.

METHODSLuminex flow cytometry were used to identify 10 MICA antibodies and evaluate the antibody specificity in 98 uremic patients positive or negative for anti-MICA antibodies undergoing kidney transplantation. The factors contributing to MICA sensitization were analyzed, and the incidence of acute rejection and graft function recovery time were compared between the positive and negative cases for anti-MICA antibodies.

RESULTSOf the 98 uremic patients, 16 (16.3%) were positive for anti-MICA antibodies. The positive and negative cases showed significant differences in the history of blood transfusion, pregnancy, transplantation, and PRA status (P<0.05). In the 38 renal transplant recipients, 6 experienced acute graft rejection, which was reversed by methylprednisolone pulse therapy; of the 10 recipients positive for anti-MICA antibodies, 4 showed acute graft rejection as compared to 2 out of the 28 recipients negative for anti-MICA antibodies (P=0.031). The cases positive for anti-MICA antibodies showed a significantly longer graft function recovery time than the negative cases (14.6∓4.7 vs 8.2∓4.5 days, P=0.001).

CONCLUSIONSBlood transfusion, pregnancy, and transplantation all contribute to the production of anti-MICA antibodies. Patients positive for anti-MICA antibodies may require strict HLA matching and more potent immunosuppressive drugs to prevent renal graft rejection and improve graft survival.

Adult ; Antibodies, Anti-Idiotypic ; immunology ; Antibody Specificity ; Blood Transfusion ; Female ; Genes, MHC Class I ; immunology ; Graft Survival ; Histocompatibility Antigens Class I ; immunology ; Histocompatibility Testing ; Humans ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Pregnancy ; Risk Factors ; Uremia ; immunology ; surgery

Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea.
Adult ; Aged ; Female ; Genes, MHC Class I ; Genotype ; HLA-C Antigens/genetics ; Hepacivirus/immunology ; Hepatitis C, Chronic/*genetics/immunology ; Humans ; Killer Cells, Natural/immunology/virology ; Male ; Middle Aged ; Receptors, KIR/*genetics/immunology ; Republic of Korea ; T-Lymphocyte Subsets/immunology

OBJECTIVEThe purpose of this study was to examine the expression of human major histocompatibility complex-I at different degrees of dysplasia leukoplakia, and to investigate local immune status and discuss their associations with oral leukoplakia.

METHODSThe monoclonal antibody of MHC class I antigen was employed in this study. There were 55 oral leukoplakias, 31 primary oral squamous cell carcinomas and 28 histologically normal oral epithelia were detected for the presence of the MHC class I molecule by using immunohistochemistry method.

RESULTSThe MHC class I antigen expression of the severe dysplasia and oral squamous cell carcinoma was significantly lower than that of the normal epithelia (P < 0.05). But their expression did not show statistically difference between the normal epithelia and other groups of oral leukoplakia (P > 0.05).

CONCLUSIONThe expression levels of the MHC class I antigen is reduced in oral leukoplakia, particularly in severe dysplasia oral leukoplakia, it is relevant to the degree of dysplasia.

Antibodies, Monoclonal ; Carcinoma, Squamous Cell ; genetics ; Genes, MHC Class I ; Histocompatibility Antigens Class I ; genetics ; Humans ; Immunohistochemistry ; Leukoplakia, Oral ; genetics ; Mouth Neoplasms ; genetics

OBJECTIVETo observe the effects on antitumor activity of mouse NK cells and the mixed lymphocyte reaction with blocking the interaction between the inhibitory Ly49 receptor on mouse NK cell and MHC-I molecules on target cells with monoclonal antibody.

METHODSNK cells were isolated from splenocytes of C57BL/6J mouse with immunomagnetic method. YAC-1 and M1 cells were used as target cells, the cytotoxicity of NK cells was examined with mixed lymphocyte reaction before and after treatment of anti-Ly49 monoclonal antibody.

RESULTThe cytotoxicity of NK cells to M1 cell was significantly augmented (10.7% +/- 0.5% compared with 84.4 % +/- 2.9%), and the clone-forming capacity of M1 cell was inhibited remarkably (8.2 % +/- 2.2% compared with 94.0% +/- 3.3%) with the increase of concentration of the antibody (0 approximate, equals 60 microg/ml) (P <0.05). The difference of cytotoxicity to YAC-1 cells was only found between 0 microg/ml and 60 microg/ml groups (P <0.05). In mixed lymphocyte reaction, after pretreated with antibody, the proliferation of splenocytes of BALB/C mouse was inhibited (0.398 +/-0.025 compared with 0.128 +/- 0.014), and statistical difference was observed only between antibody groups of 0 microg/ml and 60 microg/ml (P<0.05).

CONCLUSIONBlocking the inhibitory Ly49 receptor on NK cells with monoclonal antibody augments the cytotoxicity to target cells.

Animals ; Antibodies, Monoclonal ; immunology ; pharmacology ; Cell Proliferation ; Cells, Cultured ; Female ; Genes, MHC Class I ; Killer Cells, Natural ; immunology ; Lymphocyte Culture Test, Mixed ; Lymphoma ; immunology ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; NK Cell Lectin-Like Receptor Subfamily A ; immunology ; Spleen ; cytology ; immunology

This study was performed in order to characterize the types of the infiltrating cells, and the expression profiles of major histocompatibility complex (MHC) class I and membrane attack complex (MAC) in patients with inflammatory myopathies and dysferlinopathy. Immunohistochemical stains were performed using monoclonal antibodies against several inflammatory cell types, MHC class I, and MAC in muscles from inflammatory myopathies and dysferlinopathy. There was significant difference in the types of infiltrating cells between polymyositis (PM), dermatomyositis (DM), and dysferlinopathy, including significantly high CD4+/CD8+ T cell ratio and B/T cell ratio in DM. In dysferlinopathy, CD4+ T cells were the most abundant and the proportions of infiltrating cell types were similar to those of DM. MHC class I was expressed in muscle fibers of PM and DM regardless of the presence of inflammatory infiltrates. MAC was expressed in necrotic fibers and vessels of PM and DM. One patient with early stage DM had a MAC deposits on endomysial capillaries. In dysferlinopathy, MAC deposit was also observed on the sarcolemma of nonnecrotic fibers. The analysis of inflammatory cells, MHC class I expressions and MAC deposits may help to differentiate dysferlinopathy from idiopathic inflammatory myopathy.
Adult ; Aged ; *Dermatomyositis/immunology/pathology ; Female ; Genes, MHC Class I ; Humans ; Male ; *Membrane Proteins/genetics/immunology ; Middle Aged ; Muscle Fibers, Skeletal/cytology/immunology/pathology ; *Muscle Proteins/genetics/immunology ; *Muscular Dystrophies, Limb-Girdle/immunology/pathology ; *Myositis/immunology/pathology ; *Polymyositis/immunology/pathology ; T-Lymphocytes/cytology/immunology/pathology ; Young Adult

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue outside the uterus, causing diverse diseases, including infertility, pelvic pain, dysmenorrhea, and constipation. While there is a growing body of evidence that genetic and immunologic factors play important roles in the pathogenesis of the disease, HLA-A, B antigens have been reported to be associated with the risk of endometriosis in the Japanese population. This study was performed to determine whether the susceptibility to advanced endometriosis is also associated with HLA-A, B antigens in the Korean population, which is the closest ethnic group to Japanese. METHODS: We recruited 50 Korean patients with advanced endometriosis confirmed by surgical and histolological examinations. Distribution of HLA-A and B antigens was compared with that of 200 unrelated ethnically matched individuals. HLA-A and B genotyping was carried out using a PCRsequence specific oligonucleotide hybridization method. RESULTS: An increased frequency of B39 was observed in endometriosis patients compared with control subjects, but the difference was not statistically significant after correcting for multiple comparisons (4.0% patients vs 0.8% controls, OR=5.5, 95% CI=1.21-25.04, P=0.03, P(c)=not significant). No significant differences were found between the patients with endometriosis and the general control group with regards to the distribution of other HLA-A and B antigens. CONCLUSIONS: The findings of the present study suggest that the susceptibility to advanced endometriosis, unlike in the Japanese population, is not associated with HLA-A, B antigens in the Korean population.
Alleles ; Endometriosis/*genetics ; Female ; Gene Frequency ; *Genes, MHC Class I ; *Genetic Predisposition to Disease ; HLA-A Antigens/*genetics ; HLA-B Antigens/*genetics ; Humans ; Korea