No abstract available.
HLA-A2 Antigen* ; Isoelectric Focusing*

The pathogenesis of systemic lupus erythematosus (SLE) appears to be multifactorial, including both genetic and environmental influences. The genetic factor of SLE is well known to have an important role in the pathogenesis based on epidemiological analysis and studies of monozygotic twins. The disease occur. more commonly in first degree relatives and may affect multiple persons in single families. We report a family in which two sisters developed systernic lupus erythematosus. The clinical, laboratory and histopathological findings showed characteristic features of systemic lupus erythematosus. HLA testing revealed that the two sisters shared common HLA-DR15(2)and HLA-A2.
HLA-A2 Antigen ; Humans ; Lupus Erythematosus, Systemic* ; Siblings* ; Twins, Monozygotic

In order to evaluate association of particular HLA typing with certain uveitis in Korean population, HLA antigens were analyzed in 114 uneitis patients(acute anterior uveitis: 32 cases, Behcet`s disease: 25 cases, intermediate uveitis: 19 cases, Vogt-Koyanagi-Harada (V-K-H) syndrome: 10 cases, retinal vasculitis: 12 cases, Eale`s disease: 3 cases, posterior uveitis: 9 cases, pan.uveitis: 4 cases). The stronger association between acute anterior uveitis and HLA-B27 was statistically significant, and this result was similar to reports in other ethnic groups. Also, the association between V-K-H syndrome and HLA-DR4 showed same results. But the high frequency of HLA-DR7 in the patients with V-K-H syndrome was unque in patients of Korean popjlation and statistically significant. The association between HLA-A2 and posterior uveitis was high in patients of Korean population and statistically significant. Behcet`s disease was stronger association with HLA-B51 but not statistically significant and much weaker association than reports in Japanese group. Although many similarities of associations between particular uveitis and HLA typing were detected as compared with other ethnic groups, distinctive HLA associations were demonstrated in Korean population. Additional cases and long-term follow-up are required to confirm the association with HLA typing and the relationship with prognosis including clinical and laboratory variabilities.
Asian Continental Ancestry Group ; Ethnic Groups ; Follow-Up Studies ; Histocompatibility Testing ; HLA Antigens ; HLA-A2 Antigen ; HLA-B27 Antigen ; HLA-B51 Antigen ; HLA-DR4 Antigen ; HLA-DR7 Antigen ; Humans ; Prognosis ; Retinal Vasculitis ; Uveitis* ; Uveitis, Anterior ; Uveitis, Intermediate ; Uveitis, Posterior

PURPOSE: Immune pathophysiology of aplastic anemia (AA) has been indirectly inferred from responses to immunosuppressive agents. An association between AA and HLA-A2, or HLA-DR2 (its serologic split, HLA-DR15; or its molecular correspondents, DRB1*1501) has been implicated. The presence of HLA-DR15 (including DR2 or DRB1*15) has been closely associated with a favorable response to immunosuppression in AA. This study was aimed to characterize Korean patients with AA by determining the association with certain HLA alleles, such as HLA-DR2 or HLA-A2, and their implications in terms of the response to immunosuppression. METHODS: One-hundred eighteen children with AA from 10 university hospitals between 1990 and 2001 were enrolled in this multicenter, retrospective study. Among them, HLA data were available from 80 patients. Tests of proportions were used to compare allelic frequencies. RESULTS: The frequency of HLA-A2 (58.8%) or HLA-DR2 (24.7%) in AA was not significantly different from those of the controls. Analysis of the patients treated with immunosuppression (N=86) showed that, 50.0% of patients showed a response, including 16.0% of complete response at 6 months. The presence of DR2 allele did not portend a favorable response to immunosuppressive therapy. CONCLUSION: Unlike Western countries, the association of AA with certain HLA alleles was not documented in the Korean population. Moreover, the presence of HLA-DR2 did not predict a favorable response to immunosuppression. This peculiar characteristics of Korean AA needs to be investigated whether these findings reflect ethnic differences, different contribution of immune-mediated AA, different immune mechanisms, or mere limitation by number of study patients.
Alleles* ; Anemia, Aplastic* ; Child* ; HLA-A2 Antigen ; HLA-DR2 Antigen ; Hospitals, University ; Humans ; Immunosuppression ; Immunosuppressive Agents ; Retrospective Studies

There have been reports between Stevens-Johnson syndrome (SJS)induced by methazolamide treatment and genetic background especially in Japanese and Korean descent.We report 6 cases of SJS and the results of HLA (human leukocyte antigen)typing that suggest a relationship between genetic background and SJS induced by methazolamide treatment. We observed 6 patients as the subjects of this research, who had been suffering from SJS induced by methazolamide treatment at the Department of Ophthalmology, Catholic University.SJS appeared about 2 weeks after the patient started taking methazolamide (100 or 200 mg/d).After 15~30 days of treatment, they recovered with no serious complication.The results of HLA typing carried out 6 patients that all of the patients had HLA-A2, 5 patients were HLA-Cw1 and HLA-B59. Methazolamide should be carefully prescribed in patients of Japanese or Koreans descent and should not prescribe sulfonamide in SJS patients. A further systematic research on more cases is required to explaining ethnic peculiarity of the syndrome.
Asian Continental Ancestry Group ; Histocompatibility Testing ; HLA-A2 Antigen ; Humans ; Leukocytes ; Methazolamide* ; Ophthalmology ; Stevens-Johnson Syndrome*

OBJECTIVETo construct vitiligo-specific HLA-A*0201-peptide tetramers and to apply the constructed tetramers in detection of vitiligo-specific cytotoxic T lymphocytes (CTL).

METHODSProteins HLA-A0201*-BSP and β2M were obtained by effective prokaryotic expression. The purified proteins were refolded with vitiligo antigen peptides MelanA 26-35, gp100 209-217, and tyrosinase 1-9, respectively to form HLA-A*0201-peptide complex. The complex was biotinylated by BirA enzyme and purified by gel-filtration chromatography. The tetramers were generated by mixing the complex with phycoerythrin (PE)-streptavidin at a ratio of 4∶1 and identified by Dot-blot assay. The capacity of tetramer to detect vitiligo-specific CTL was analyzed by flow cytometry.

RESULTSThe biotinylation of vitiligo-specific HLA-A*0201-peptide tetramers were successfully performed by Dot-blot. Flow cytometry analysis indicated that the tetramer effectively bound to specific CTL from peripheral blood of patients with vitiligo.

CONCLUSIONThree kinds of biotinylated vitiligo-specific HLA-A*0201-peptide tetramers have been constructed successfully. The tetramer can detect antigen specific CTL from patients with vitiligo.

Biotinylation ; Flow Cytometry ; HLA-A2 Antigen ; Humans ; Peptides ; T-Lymphocytes, Cytotoxic ; cytology ; Vitiligo ; diagnosis ; immunology

OBJECTIVE: Behcet? disease (BD) is a chronic inflammatory disorder affecting several organs. The etiology of BD remains unclear, although genetic factors, infectious agents, and immune mechanisms have been studied. The association of BD with certain genetic factors, especially HLA-B51 antigen, is well known in some geographical areas. Nevertheless, the familial occurrence of BD is rare. In this paper, HLA phenotype was evaluated in one family member showing the clustering of BD. METHODS: The serological tissue typing of HLA class I and class II antigens was performed by standard National Institutes of Health microlymphocytotoxicity method in seven family members in which four siblings were affected by BD. The diagnosis of BD was established by the criteria of the International Study Group of BD in these four siblings. RESULTS: In this family study, all members had HLA-A2 and DQ3 antigens. Although HLA-B51 antigen was positive in six out of seven family members, BD was developed in three of the six having HLA-B51 antigen. Three siblings had the exact same HLA phenotype. However, only one person had BD among three siblings with identical HLA phenotype. In addition, all siblings who developed erythema nodosum-like lesion had HLA-B51 antigen. CONCLUSION: This family suggests that the familial clustering of BD may not be explained solely by a susceptible HLA phenotype. The environmental factor or other genetic factors besides HLA-B51 might play a role in the development of BD. Furthermore, more studies and information will be needed to clarify the role of A2 and DQ3 antigens in BD.
Diagnosis ; Erythema ; Histocompatibility Antigens Class II ; Histocompatibility Testing ; HLA Antigens* ; HLA-A2 Antigen ; HLA-B51 Antigen ; Humans ; National Institutes of Health (U.S.) ; Phenotype ; Siblings

HLA-A2 is present at high frequency in most populations, as identified by serological and biochemical means. The values of these methods are limited by their failures to discriminate the products of the known allelic HLA-A02 variants. The great majority of genetic polymorphism which defines the allelic variants is found in exons 2 and 3 of the HLA-A02 gene. These exons encode the a-1 and a-2 domains of the HLA class I molecules, and the variation within the genes may influence the peptide binding specificity of the gene products of each allele. To determine the 17 known alleles of HLA-A02 an ARMS-PCR was developed. We applied this ARMS-PCR to 10 standard cell lines and we confirmed the specificity and sensitivity of this method. We defined the HLA-A 02 subtypes in 146 healthy Koreans who were serologically identified as HLA-A2. Five subtypes out of the 17 known A02 alleles were detected (A'0201, 0203, 0206, 0207, '0210) and A'0201 was most frequent (53.4%) and A'0206, '0207, '0203, 0210 (37.0%, 18.5%, 2.7%, 2.1%), were followed respectively. By linkage disequilibrium analysis with HLA-B alleles, A*02 subtypes were defined to be associated with many B alleles (B27, 35, 38, 39, 46, 52, 60, and 61). It is suggested that these findings may be helpful for the selection of patients for the specific immunotherapy with HLA-A02 restricted peptide vaccines and for the unrelated bone marrow transplantation in Korean.
Alleles ; Bone Marrow Transplantation ; Cell Line ; Exons ; HLA-A Antigens ; HLA-A2 Antigen ; HLA-B Antigens ; Humans ; Immunotherapy ; Linkage Disequilibrium ; Polymorphism, Genetic ; Sensitivity and Specificity ; Vaccines, Subunit

BACKGROUND: Graves' disease(GD) is an organ-specific autoimmune disorder that is inherited as a complex trait. At present three loci, namely the human leukocyte antigen(HLA), the cytotoxic T lymphocyte antigen-4(CTLA-4) and a thyroid stimulating hormone receptor(TSHR) are the only well-known genetic determinants for GD. To understand the mechanisms underlying the development of GD, we investigated the relationship of HLA alleles, polymorphisms of CTLA-4 gene and the tumor necrosis factor(TNF)-beta gene, with the disease susceptibility. METHODS: Fifty-two Korean children with GD(45 girls and 7 boys), and 119 healthy children, were investigated in this study. The HLA alleles were determined by a standard lymphocyte microtoxicity technique, ARMS-PCR(Amplification Refractory Mutation System-Polymerase Chain Reaction), PCR-SSP(Sequence Specific Primer) and PCR-SSOP(Sequence Specific Oliogonucleotide Probe) method. The CTLA-4 gene polymorphism was analyzed by PCR-SSCP(Single Strand Conformation Polymorphism), and the TNF-beta gene polymorphism by PCR-RFLP(Restriction Fragment Length Polymorphism). RESULTS: (1) The frequencies of HLA-A2, B46, DRB1*08 and DPB1*0202 were significantly increased, and those of HLA-A24, DQA1*01 and DQB1*05 were significantly decreased, in the GD patients compared to the control subjects. (2) A significant difference in the distributions of the AA, AG, and GG genotypes of the CTLA-4 exon 1 were observed between the GD patients and the control subjects, and a significant increase in the frequency of the G (alanine) allele was seen in the GD patients compared with the control subjects(84.6% vs 63.4%; RR=3.2; p<0.0001). A significant difference in the distributions of the AA, AG, and GG genotypes of the CTLA-4 exon 1 was observed between the GD patients with and without exophthalmos. A significant increase in the frequency of the G allele was seen in the GD patients with exophthalmos compared to those without(94.0% vs 75.9%; RR=7.0; p<0.05). (3) No significant difference in the distributions of the 1/1, 1/2 and 2/2 genotypes, and the 1 and 2 alleles of TNF-beta was observed between the GD patients and the control subjects. No significant difference in the distributions of the 1/1, 1/2, and 2/2 genotypes and the 1 and 2 alleles of TNF-beta were observed between the GD patients with or without exophthalmos but a significant increase in the frequency of the 2/2 allele was seen in the GD patients having TSHRAb > or =45% compared with GD patients having TSHRAb <45%(37.5% vs 3.6%; RR=14.8; p<0.01). CONCLUSION: These data suggest that HLA-A2, B46, Cw*0102, DRB1*08 and DPB1*0202 are markers for disease susceptibility, and that HLA-A24, DQA1*01 and DQB1*05 are markers for disease protection, in Korean children with GD. This study showed that the CTLA-4 gene polymorphism was an additional marker of susceptibility in the GD patients, and was associated with exophthalmos, and that the TNF-beta gene polymorphism was associated with the TSHRAb activity.
Alleles ; Child* ; Disease Susceptibility* ; Exons ; Exophthalmos ; Female ; Genotype ; Graves Disease* ; HLA-A2 Antigen ; HLA-A24 Antigen ; Humans ; Leukocytes ; Lymphocytes ; Lymphotoxin-alpha* ; Necrosis ; Thyrotropin

We examined the immunogenicity of H-2 class I-restricted and HLA-A2-restricted epitopes through peptide immunization of HLA-A2-transgenic mice that also express mouse H-2 class I molecules. All four of the tested epitopes restricted by H-2 class I robustly elicited T-cell responses, but four of seven epitopes restricted by HLA-A2 did not induce T-cell responses, showing that HLA-A2-restricted peptide epitopes tend to be poorly immunogenic in HLA-A2-transgenic mice. This finding was confirmed in HLA-A2-transgenic mice infected with a recombinant vaccinia virus expressing hepatitis C virus proteins. We examined the precursor frequency of epitope-specific naive CD8+ T cells in HLA-A2-transgenic and conventional C57BL/6 mice and found that the poor immunogenicity of HLA-A2-restricted peptide epitopes is related to the paucity of naive CD8+ T-cell precursors in HLA-A2-transgenic mice. These results provide direction for the improvement of mouse models to study epitope repertoires and the immunodominance of human T-cell responses.
Animals ; Epitopes* ; Epitopes, T-Lymphocyte ; Hepacivirus ; HLA-A2 Antigen ; Humans ; Immunization ; Mice* ; Precursor Cells, T-Lymphoid* ; T-Lymphocytes ; Vaccinia virus