Analysis of Gene Recombination between HLA-B and -DRB1, HLA-DQB1 and -DPB1 Loci / 中国实验血液学杂志

OBJECTIVE@#To investigate the recombinations within the human leukocyte antigen (HLA) region in two families.@*METHODS@#Genomic DNA was extracted from the peripheral blood specimens of the different family members. HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci were genotyped using polymerase chain reaction-sequence specific oligonucleotide probing technique (PCR-SSO) and next-generation sequencing technique. HLA haplotype was determined by genetic analysis of the pedigree.@*RESULTS@#The haplotypes of HLA-A*11:01~C*03:04~B*13:01~DRB1*12:02~DQB1*03:01~DPB1*05:01:01G and HLA-A*03:01~C*04:01~B*35:03~DRB1*12:01~DQB1*03:01~DPB1*04:01:01G in the family 1 were recombined between HLA-B and HLA-DRB1 loci, which formed the haplotype of HLA-A*11:01~C*03:04~B*13:01~DRB1* 12:01~DQB1*03:01~DPB1*04:01:01G. The haplotypes of HLA-A *02:06~C*03:03~B*35:01~DRB1*08:02~DQB1*04:02~ DPB1*13:01:01G and HLA-A *11:01~C*07:02~B*38:02~DRB1*15:02~DQB1*05:01~DPB1*05:01:01G in the family 2 were recombined between HLA-DQB1 and HLA-DPB1 loci, which formed the haplotype of HLA-A*02:06~C*03:03~B*35:01~ DRB1*08:02~DQB1*04:02~DPB1*05:01:01G.@*CONCLUSION@#The gene recombination events between HLA-B and -DRB1, HLA-DQB1 and -DPB1 loci were found respectively in two Chinese Han families.

Study on the extensibility of platelet donor gene database in Shaanxi / 中国输血杂志

【Objective】 To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. 【Methods】 The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. 【Results】 Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P<0.05). With a database size of the existing platelet donor bank adding the first and second echelons (n=4 955), there was a 69.02% probability of matching at least one donor with matching HLA-A-B phenotype. When considering the matching ABO and HPA phenotypes, the probability of finding at least one donor with fully matching HLA, HPA and ABO isotype (type B as an example) was 48. 73%. 【Conclusion】 The three groups of whole blood donation, apheresis platelet donation and marrow donation in Xi'an area have a large cross-distribution. Compared with expanding the storage capacity from scratch, the active blood donors in CMDP database are the largest back-up force of platelet donors. While expanding the effective storage capacity, it can minimize the cost of building platelet donor bank and the demand for resources.

The capacity evaluation and utilization strategy of the platelet donor database with known HLA/HPA genotype in Shaanxi / 中国输血杂志

【Objective】 To evaluate the appropriate optimal capacity and matching probability of the platelet donor database with known HLA/HPA genotype in Shaanxi aera, and provide data support for subsequent construction, maintenance and application of the local platelet donor database. 【Methods】 A total of 11 755 individuals from the Shaanxi Branch of China Marrow Donor Program, 401 and 249 unrelated random platelet donors in Shaanxi aera were enrolled to the population study of HLA-A, -B polymorphisms, HPA genotyping and CD36 antigen expression, respectively. The frequencies of HLA-A, -B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software; matching probability and capacity evaluation of platelet donor database was conducted according to the phenotypic frequencies. 【Results】 The population genetic and phenotypic polymorphisms data of HLA-A, -B and HPA1-6, 10, 15, 21 in Shaanxi aera were obtained. The frequency of CD36 type Ⅰ or Ⅱ deficiency was 0.40%(1/249). According to the subsequent calculating and deriving, with a database size of 194 donors, the patient having approximate 95% probability could achieve matching of HPA1-6, 10, 15, 21 genotype. With a database size of 1500 donors, there is a 95% probability of matching at least one donor with HLA-A-B phenotype frequency >0.002 or haplotype frequency >0.001; meanwhile, the probability of matching a cross-reactive group donor should be 44.95%-97.57%. Based on database size of 8 856 and 15 033, the probabilities of matching HLA-A, -B phenotype were about 80% and 90%, respectively. 【Conclusion】 The differences in the distribution of HLA/HPA polymorphism in different regions make the establishment mode and optimal capacity of platelet donor database different. It is necessary to apply a variety of platelet matching transfusion strategies to expand the range of donor selection, thereby effectively reducing the database construction cost and resource requirements.

New progress on diagnosis and treatment of acute cellular rejection after lung transplantation / 器官移植

Acute cellular rejection (ACR) is a common complication after lung transplantation, which is mainly caused by the immune response of T lymphocytes recognizing the major histocompatibility complex on the cellular surface of grafts. It is currently considered as the main pattern of acute rejection. ACR is not only a direct cause of death of recipients, but also a high-risk factor for chronic rejection after lung transplantation. Nevertheless, it is a challenging task to deliver the diagnosis and treatment of ACR following lung transplantation. In this article, new progresses on the risk factors, pathogenesis, diagnosis and treatment of ACR in lung transplant recipients were summarized, aiming to improve the diagnostic and treatment efficiency of ACR and prolong the survival of recipients.

Association of HLA-DRB1, -DQB1, -DPB1 alleles and haplotype polymorphisms with acute myeloid leukemia (non-M3) in northern Han population / 中国输血杂志

【Objective】 To explore the association of HLAII(-DRB1, -DQB1, -DPB1) alleles and haplotypes polymorphisms with acute myeloid leukemia (AML) in northern Han population. 【Methods】 A total of 308 AML (non-M3) patients (patient group) and 824 unrelated healthy bone marrow donors (control group) were genotyped at a high-resolution level using polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) with Ion Torrent S5 platform and sequence specific oligonueleotide probes (SSO) with LABScan® 3D platform. Frequencies of HLA II alleles and haplotypes were calculated with Arlequin 3.5.2.2 software. The odds ratio (OR) of AML was also calculated for case-control study. 【Results】 By χ2 test and correction, an increased frequency of HLA-DRB1*07∶01(14.61% vs 9.53%, P<0.01), HLA-DQB1*02∶02(12.82% vs 8.31%, P<0.01), HLA-DQB1*06∶02(11.53% vs 8.74%, P<0.05) and HLA-DPB1*17∶01(5.84% vs 3.16%, P<0.01) among AML patients was discovered in significant comparison with the control group. After Bonferroni correction, the frequency of HLA-DRB1*07∶01(Pc<0.05), HLA-DQB1*02: 02(Pc<0.05) and HLA-DPB1*17∶01(Pc<0.05) in AML patients were still higher than those in the control group, which had a strong positive correlation with AML (OR=1.62 (95% CI=1.23~2.14), 1.62(95% CI=1.21~2.18) and 1.91(95% CI=1.23~2.94), respectively. The frequency of two loci haplotype HLA-DRB1*07∶01-DQB1*02∶02 in AML patients was still higher than that of the control group after Bonferroni correction (12.66% vs 8.19%, Pc<0.05). The frequency of the 3 loci haplotype HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01, as a susceptible haplotype of AML, was higher than that of the control group and was strongly correlated with AML. 【Conclusion】 The data on the association of HLA II (-DRB1, -DQB1, -DPB1) alleles and haplotype polymorphisms with AML in northern Han populations was obtained in this study. HLA-DRB1*07∶01, HLA-DQB1*02∶02, HLA-DPB1*17∶01 and the HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01 haplotype are the risk genes and susceptible extended haplotype for AML. The risk prediction based on HLA haplotype might be more accurate than that based on single allele.

Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation / 器官移植

Regulatory T cell (Treg) is a subset of T cells that negatively regulates immunity and has the function of inhibiting rejection. The specific modification of Treg by chimeric antigen receptor (CAR) technology can successfully chime donor-specific antigen onto the surface of Treg, thus regulating the immune function of the body in a real-time manner. It provides a novel and promising therapeutic option for inducing immune tolerance. In this article, research progresses on Treg in immune related diseases, main difficulties in the realization of CAR-Treg technology and its role in inducing transplantation immune tolerance were reviewed, and the opportunities and challenges of CAR-Treg application in the field of organ transplantation are prospected.

Experimental study on the in vitro induction of regulatory T cells by umbilical cord mesenchymal stem cells with positive human leukocyte antigen-G / 器官移植

Objective To explore the effect of umbilical cord mesenchymal stem cells with positive human leukocyte antigen(HLA)-G on inducing the production of regulatory T cells(Treg) in vitro.Methods Umbilical cord mesenchymal stem cells were isolated from umbilical cord of neonates. PEGFP-N1-HLA-G plasmid was transfected into the human umbilical cord mesenchymal stem cells by liposome transfection, as PEGFP-N1-HLA-G group. PEGFP-N1 empty vector plasmid was transfected into the human umbilical cord mesenchymal stem cells, as PEGFP-N1 group. The human umbilical cord mesenchymal stem cells without empty vector under the same conditions were set as blank control group. Markers of the umbilical cord mesenchymal stem cells were detected using flow cytometry. The expression of HLA-G protein in each group of cells was identified by Western Blot. After mixed-culturing with CD4+T cells in peripheral blood of healthy subjects for 24 h and 48 h, the proportion of CD4+CD25+Foxp3+Treg in total T cells of each group was detected by flow cytometry. Results CD45, CD34 and HLA-DR presented negative expression on umbilical cord mesenchymal stem cells, while CD29, CD44 and CD105 presented positive expression. HLA-G protein could be expressed in the PEGFP-N1-HLA-G group, which had statistically significant difference compared with the blank control group and PEGFP-N1 group (both P<0.01). After PEGFP-N1-HLA-G group and CD4+T cells were mixed-cultured for 24 h and 48 h, CD4+CD25+Foxp3+Treg accounted for (15.3±1.9)% and (14.3±2.1)% of the total T cells respectively, both of which presented statistically significant difference compared with the blank control group and PEGFP-N1 group (all P<0.05). Conclusions Umbilical cord mesenchymal stem cells with HLA-G gene modified can effectively induce the production of CD4+CD25+Foxp3+Treg in vitro.

Clinical observation on the removal of donor specific antibody by double filtration plasmapheresis in renal transplant recipients / 器官移植

Objective To investigate the effect of double filtration plasmapheresis (DFPP) upon the removal of donor specific antibody (DSA) in highly sensitized recipients with renal transplantation. Methods Four highly sensitized recipients undergoing renal transplantation received 7 cycles of DFPP. Luminex technology was adopted to monitor the changes of DSA. Clinical efficacy, incidence of acute rejection and adverse reactions were observed. Results After DFPP, the DSA MFI [1036 (0-4113)] was significantly declined than that before treatment [6446 (2999-12905), Z= -2.503, P=0.012]. No hyperacute rejections occurred in four highly sensitized recipients undergoing renal transplantation.Acute rejection was noted in one case, which was mitigated by postoperative DFPP and adjustment of immunosuppressive agents. During postoperative follow-up, the function of transplant kidney was normal and no rejection reactions occurred. The level of albumin was decreased after DFPP. Conclusions DFPP can effectively remove the DSA in the recipients.It is an efficacious and safe approach to prevent the incidence of acute rejections in highly sensitized recipients after renal transplantation.

Effect of anti-HLA antibody detected by Luminex testing on clinical prognosis of renal transplantation ;recipients / 器官移植

Objective To investigate the value of anti-human leukocyte antigen (HLA)antibody level detected by Luminex testing in predicting clinical prognosis of renal transplantation recipients. Methods A total of 1 105 patients scheduled to undergo renal transplantation (354 successfully undergoing renal transplantation)in the 181st Hospital of People's Liberation Army from June 2013 to November 2015 were selected. The serum samples were collected from 1 923 cases before and after renal transplantation. The positive rate and fluorescent intensity of anti-HLA antibody were detected by Luminex testing before and after renal transplantation. The renal function of recipients was also evaluated after renal transplantation. Results Prior to renal transplantation,51.0%(546/1 071)of serum samples were positive for anti-HLA antibody,including 26.0%(279/1 071)positive for anti-HLAⅠantibody,24.9%(267/1 071)positive for anti-HLAⅡantibody and 11.4% (122/1 071 )positive for both anti-HLA Ⅰ and anti-HLA Ⅱ antibodies. Among 354 patients undergoing renal transplantation,59 (17%)were positive for anti-HLA antibody after renal transplantation,including 25 (4 newly positive after surgery)positive for anti-HLAⅠantibody,15 (1 newly positive after surgery)positive for anti-HLAⅡantibody and 19 (4 newly positive after surgery)positive for both anti-HLA Ⅰ and anti-HLA Ⅱ antibodies. During subsequent follow-up,13 patients positive for anti-HLAⅠantibody,5 positive for anti-HLAⅡantibody and 1 1 positive for both anti-HLA Ⅰ and anti-HLA Ⅱ antibodies developed transplant kidney dysfunction. All patients newly positive for anti-HLA antibody after renal transplantation presented with transplant kidney dysfunction. Conclusions Luminex testing can perform dynamic detection of the positive rate of anti-HLA antibody,which is important in predicting clinical prognosis of recipients after renal transplantation.

Unrelated hematopoietic stem cell registry and the role of the Hematopoietic Stem Cell Bank

BACKGROUND: The hematopoietic stem cell bank has been actively recruiting registrants since 1994. This study systematically reviews its operations and outcomes over the last 20 years. METHODS: Retrospective data on a total of 47,711 registrants were reviewed. Relevant data were processed using PASW Statistics for Windows, version 18.0. RESULTS: As of 2013, the Korean Network for Organ Sharing database contained 265,307 registrants. Of these, 49,037 (18%) registrants committed to hematopoietic cell donation from 1994 to 2013. Fifty-seven percent of the registrants were men, and 43% were women. The reasons for opting out of the registry included refusal to donate (70%), family refusal (28%), and others (2%). The donation willingness of registrants was significantly higher than those who refused to receive a mail to confirm their continued enrollment (χ2=6.103, P=0.013). The bank successfully coordinated a total of 512 donors among newly matched donors from 1995 to 2013, of which the bone marrow and peripheral blood stem cell accounted for 40.8% and 59.2% of the total donations, respectively. CONCLUSION: Our recruitment activities focus on promoting voluntary registration and the importance of updating personal contact information. We expect that these data may be useful for diverse studies and demonstrate the positive impacts on the donation program.

Cervical carcinoma HLA gene susceptibility and NK cell receptor immune re-sponses / 中国免疫学杂志

Objective:To investigate the effect of HLA genetic susceptibility and NK cell receptors and immune response on the occurrence and development of the Cervical cancer.Methods: Select the 200 patients confirmed by the pathological biopsy in our hospital from January 2013 to January 2014 as the observation group.At the same time,randomly select the 200 healthy women as the control group.Both of them blood 2 ml peripheral blood,sample the cervical cell from the observation group.Having the cytological ob-servation and the DNA′s probe of the HPV,observe two group′s HPV infection rates and HLA′s parting.Results: The HPV infection rates of the observation group is 91%,and the rates of the control group is 16%.The differences between them were all significant(P<0.05).The HLA-KIR*1003,HLA-KIR*14,HLA-KIR*17,HLA-KIR*02,HLA-KIR*12 distribution frequency of the observation group are 41%,39%,35%,15%,53%.The HLA-KIR*1003,HLA-KIR*14,HLA-KIR*17,HLA-KIR*02,HLA-KIR*12 distribution frequency of the control group are 18%,15%,14%,52%,89%.The differences between them were all significant ( P<0.05).Among them The HLA-KIR*1003, HLA-KIR*14, HLA-KIR*17 distribution frequency of the observation group are significantly higher than the control group, HLA-KIR*02 , HLA-KIR*12 distribution frequency of the observation group are significantly lower than the control group.Conclusion:During the occurrence and development of the Cervical cancer,the HLA-KIR*1003,HLA-KIR*14,HLA-KIR*17 may be the risk factors for the Cervical cancer;the HLA-KIR*02,HLA-KIR*12 may be the protective factors for the Cervical cancer.

Increased soluble HLA-DRB1 in B-cell acute lymphoblastic leukaemia

Soluble HLA (sHLA) are potential tumour markers released in order to counter immune surveillance. sHLA-class II is less known especially in acute lymphoblastic leukaemia (ALL). This study aimed to investigate soluble, surface and allelic expression of HLA Class II (sHLA-DR) in B-cell ALL patients and compare with soluble expression in normal individuals. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to measure soluble HLA-DRB1 in plasma. Flow cytometric analysis was performed to determine median fluorescence intensity in HLA-DR surface expression. HLA-DNA typing by polymerase chain reaction, sequence specific oligonucleotides, PCRSSO was performed to determine HLA-DRB1 type in ALL samples. Results showed sHLA-DRB1 (mean+SEM) was significantly increased (p=0.001) in plasma of ALL patients (0.260±0.057 μg/mL; n=30) compared to healthy controls (0.051±0.007μg/mL; n=31) of Malay ethnicity. However, these levels did not correlate with percentage or median fluorescence intensity of HLA-DR expressed on leukemia blasts (CD19+CD34+/-CD45loHLA-DR+) or in the normal B cell population (CD19+CD34- CD45hiHLA-DR+) of patients. No significant difference was observed in gender (male/female) or age (paediatric/adult). Only a trend in reduced sHLA was observed in patients carrying HLA-DR04. These results have to be validated with a larger number of samples.

Variations in immunogenetics, human papillomavirus (HPV) infection & predisposition to cervical cancer in Indian women.

Background & objectives: Human papillomavirus (HPV) is the main causative agent for cervical cancer. Variability in host immunogenetic factors is important in determining the overall cellular immune response to the HPV infection. This study was carried out to confirm the association between human leukocyte antigen (HLA) class II alleles and cervical cancer in HPV infected women. Methods: both low and high resolution methods were used to genotype HLA class II (DRB1 and DQB1) alleles in 75 women with cervical cancer (cases) and 75 HPV positive women and 100 HPV negative women with healthy cervix (controls). odds ratio and 95% confidence interval were calculated. Co-occurring HLA alleles (haplotype) across cases and controls were also studied. Results: Significant association was found for HLA-DRB1*03(*13:01) and - DQB1*02(*02:01) with increased risk for cervical cancer. Also, HLA-DRB1*13(*13:01); -DQB1*06 and -DQB1*03:02 were significantly associated with decreased risk for cervical cancer. Haplotype analysis highlighted the significant association of HLA- DRB1*07:01-DQB1*02:02 and HLA DRB1*10:01-DQB1*05:01 with cervical cancer, while HLA-DRB1*14:04-DQB1*05:03 and DRB1*15:01-DQB1*06:01 conferred decreased risk for cervical cancer. Multivariate analysis highlighted the association of specific alleles with cervical cancer after adjusting for confounding factor age. Interpretation & conclusions: There were possible associations of specific HLA class II alleles either with risk of developing cervical cancer, or with its protection. Our results confirmed the assessment of DRB1*13 as a protective marker in HPV infection outcome. our study also revealed protective association of homozygous haplotype DRB1*15- DQB1*06 with cervical cancer.

Challenges with sensitized recipients in pediatric heart transplantation

The sensitization of patients to human leukocyte antigens prior to heart transplantation is increasingly being recognized as an important challenge both before and after the transplant, and the effects of sensitization on clinical outcomes are just beginning to be understood. Many patients are listed with the requirement of a negative prospective or virtual crossmatch prior to accepting a donor organ. This strategy has been associated with both longer waitlist times and higher waitlist mortality. An alternative approach is to transplant across a potentially positive crossmatch while utilizing strategies to decrease the significance of the human leukocyte antigen antibodies. This review will examine the challenges and the impact of sensitization on pediatric patients prior to and following heart transplantation.

Herpes simples: atualização clínica, epidemiológica e terapêutica / Herpes simplex: clinical update, epidemiology and therapeutics

Herpes é uma infecção causada por dois vírus da família Herpesviridae (herpes simples tipos 1 e 2; HSV-1 e HSV-1), que apresenta curso clínico variável e para o qual atualmente não existe cura. As manifestações da infecção por HSV-1 incluem herpes simples orofacial primário e recorrente, enquanto as do HSV-2 em geral ocorrem na forma de herpes simples genital, embora casos de lesões genitais pelo HSV-1 e orais pelo HSV-2 possam ocorrer. As infecções pelo vírus herpes simples (HSV-1 e HSV-2) representam as doenças sexualmente transmissíveis mais comuns a nível global, alcançando uma soroprevalência de 80% em adultos. Nesta revisão da literatura, abordaremos os aspectos clínicos da infecção pelo HSV, incluindo a epidemiologia, etiologia, manifestações clínicas, métodos diagnósticos e tratamento, bem como uma breve descrição da imunogenética da infecção pelo HSV

Herpes is an infection caused by two viruses in the Herpesviridae family (herpes simplex types 1 and 2; HSV-1 and HSV-2), which presents a variable clinical course and for which there is currently no cure. The manifestations of HSV-1 infection include primary and recurrent orofacial herpes simplex, while HSV-2 infection usually manifests in the form of genital herpes simplex, although cases of genital lesions from HSV-1 infection and oral lesions form HSV-2 infection can occur. Infections by the herpes simplex virus (HSV-1 and HSV-2) represent one of the most common sexually transmitted diseases globally, reaching a serum prevalence of 80% in adults. In this review of the literature, we discuss the clinical aspects of HSV infection, including epidemiology, etiology, clinical manifestations, diagnosis and treatment, as well as a brief description of the immunogenetics of HSV infection.

Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population.

AIM: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. MATERIALS AND METHODS: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. RESULTS: The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. CONCLUSION: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region.

Recipient's Killer Cell Immunoglobulin-like Receptor Genotype and Human Leukocyte Antigen C Ligand Influence the Clinical Outcome following Living Donor Liver Transplantation

PURPOSE: The design of this study was to determine the most influential factor(s) on post-transplant immunological consequences, particularly with regard to the role of killer cell immunoglobulin-like receptors (KIRs) and their ligands (type I human leukocyte antigen (HLA)) in unstable liver function. METHODS: Retrospectively collected data from 319 recipients undergoing adult living donor liver transplantation (LDLT) using a right lobe graft between January 2002 and August 2008 were analyzed. Patients were categorized according to the serum alanine transaminase (ALT) pattern; stable ALT pattern was defined as ALT pattern during 3 months post-transplantation, except for initial 2 weeks post-transplantation, in which 2 times or less additional elevation(s) of serum alanine transaminase (ALT) (> or =80 IU/L) were observed. When a serum ALT pattern showed fluctuating and/or unpredictable nature, it was defined as an unstable pattern. In addition, genetic information of KIRs and HLA-C allotypes received from 68 recipients and 59 donors was analyzed by way of polymerase chain reaction using sequence-specific primers (PCR-SSP) to determine the factor(s) influencing a serum ALT pattern. RESULTS: Among 319 LDLT recipients included in this study, the actual incidences of AR and unstable ALT pattern were 13.4% (43/319) and 42.3% (135/319), respectively. Unstable ALT pattern correlated with poorer survival following LDLT than stable pattern (P<0.000). Genetically, unstable ALT pattern was related to recipients carrying KIR2DL2(+)/KIR2DS2(+) combined with the heterogeneous HLA-C allotype (HLA-C1/C2), (relative risks 45.0, 95% confidence interval 2.160~937.321; P=0.013). CONCLUSION: This study indicates that, when performing LDLT, pretransplant determination of recipient's KIRs and HLA-C allotypes may be beneficial in coping with post-transplant immunological circumstances.

Relationship among HLA-A alleles, supertype and the susceptibility of cervical cancer / 基础医学与临床

Objective To study the relationship among HLA-A alleles, supertype, HPV infection and cervical cancer in Tu Nationality of Hubei province. Methods As a case-control surevy. The comparisons included the comparison between HPV positive cases and HPV positive women in control group, and the comparison between HPV positive cases and HPV negative women in control group. Number of cases was 100 ( HPV positive in 86) , and control was 187 ( HPV positive in 95 and HPV negative in 92). The most polymorphism of 2 and 3 exons of the HLA-A alleles were analyzed by the high-resolution typing method-sequence-based typing( SBT). Results Compar-ison between HPV positive cases and HPV positive control women. Supertype HLA-A3 (P_(corrected) = 0. 005, OR = 2. 36, 95% CI = 1. 45～3. 85) was risk factors. Comparison between HPV positive cases and HPV negative control women, HLA-A * 0206 alleles (P_(corrected)=0. 025,OR =0. 20,95% CI =0. 07～ 0. 58 ) supertype HLA-A2 ( P_(corrected) = 0.005 , OR = 0. 57 ,95% CI = 0. 37 ～ 0. 88 ) was protective factor. Supertype HLA-A3 ( P_(corrected) = 0. 005 , OR = 2. 36, 95% CI = 1. 45～3. 85) was also related to the susceptibility of cervical carcinoma. Conclusion Supertype HLA-A3 is a risk factor of cervical cancer.

Analysis of Panel Reactive Antibody in Patients Awaiting Renal Transplantation / 대한이식학회지

BACKGROUND: We performed panel reactive antibody (PRA) tests in renal transplantation candidates registered to the Korean Network for Organ Sharing (KONOS) and analyzed the results of PRA tests in relation to the results of HLA crossmatch (XM) tests and transplantation history. METHODS: From 833 patients awaiting cadaveric renal transplantation in the KONOS registry, 122 (98 patients) XM (NIH or AHG)-positive and 147 (147 patients) XM-negative serum samples were selected for PRA test. Enzyme linked immunosorbent assay (ELISA)-PRA screening test was performed and HLA antibody specificities were identified by NIH and AHG PRA methods. RESULTS: PRA positive rate was significantly higher in XM-positive group compared with XM-negative group (ELISA-PRA, 70.5% vs. 21.8%; AHG-PRA [PRA > or =10%], 73.9% vs. 9.6%). Donor specific antibodies were defined in 52.5% (64/122), whereas false positive XM results were suspected in 20.5% (25/122) of the XM-positive samples. Patients with transplantation histories showed significantly higher positive rates for ELISA-PRA (78.7% vs. 30.8%) and AHG-XM tests (78.2% vs. 29.3%). Highly sensitized patients (AHG-PRA > or =80%) showed significantly higher cumulative waiting rate (88.9% vs. 60.2% at 4 years) and longer waiting time (3.8 vs. 3.6 years) (Kaplan Meier method, P=0.037). PRA positive rate in the total renal transplantation candidates in the KONOS registry was estimated to be 33.9% for ELISA-PRA and 21.7% for AHG-PRA (PRA > or =10%), and the proportion of highly sensitized (PRA > or =80%) patients was estimated to be 5.4%. CONCLUSIONS: Pre-transplantation PRA as a routine test is needed in cadaveric renal transplantation for effective and fair allocation of organs in Korea.

Poly-peptide immunogenicity of human thyroid-stimulating hormone receptor that may cause Graves' disease / 基础医学与临床

DQA1*0501.TSHR peptides of 183～198、195～210、248～263、301～320、343～362 and 357～376 could bind with high affinity to both HLA-DR3 and HLA-DQA1*0501,all of their IC50 values less than(1 ?mol/L),but they could bind to neither HLA-DR7 nor HLA-DQA1*0201 with high affinity.Conclusion Epitopes of TSHR 183～198,195～210,248～263,301～320,343～362 and 357～376 on the TSHR extracellular domain might be the auto-antigens to cause GD.