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Abstract Introduction: Hepatitis B virus (HepB) infection is a global health problem with increasing cause of morbidity and mortality.Hemodialysis patients are especially vulnerable to HepB infection due to uremia-related immune dysfunction, frequent interventions they exposed, and health-care personnel's unsafe care. The vaccination against HepB confers the primary preventive measure. However, unresponsiveness to vaccination constitutes a major problem. Several factors can influence the immune response to vaccines but human genetic variations are thought to strongly militate the variability in vaccine responsiveness. We aimed to determine the association with specific HLA alleles and response to HepB vaccination in hemodialysis patients. Methods: The study included in-center hemodialysis patients. We retrospectively collected data regarding demographic, clinical, and laboratory features including anti-HBs antibody, antibody to hepatitis C (anti-HCV), anti-HIV, and specific HLA class I and II alleles (HLA-A, HLB, HLA-DR) from electronical medical record system. The frequencies of HLA class I and II antigens in nonresponders and responders were analyzed. Results: The most commonly observed HLA alleles in patients were DQA1*01 (%73.7), DQA1*05 (%57.9), DQB1*03 (%53.8), DQB1*05 (%38.5), and DRB1*11 (%37.3), respectively. The frequency of HLA-B40 allel was significantly higher in nonresponders (p=0.02, OR=6.25, 95%CI =1.33-29.3). HLA-DQA1*01 and HLA-DQB1*05 alleles were observed significantly more in responders (p=0.019, OR =6.9, 95% CI=1.40-33.91, andp=0.028, OR =10, 95% CI=1.12-88.91, respectively). Conclusion: This is the first study to our knowledge demonstratingthe association between antibody response to HBsAg and HLA-B40, HLA-DQA1*01, and HLA-DQB1*05 alleles in Turkish hemodialysis patients.
Resumen Introducción: La infección por el virus de la hepatitis b (VHB) constituye un problema de salud mundial con una morbimortalidad cada vez mayor.Los pacientes que reciben hemodiálisis están particularmente expuestos a una infección por el virus de la hepatitis b debido a una disfunción del sistema inmunitario relacionada con la uremia, las intervenciones a las que se someten frecuentemente y prácticas poco seguras por parte del personal de salud. La vacuna contra el VHB constituye la medida preventiva principal. Sin embargo, la falta de respuesta a la vacuna supone un gran problema. Existen varios factores que pueden influir sobre la respuesta inmunitaria a la vacuna, pero se cree que las variaciones genéticas humanas tienen una gran incidencia sobre la variación en la respuesta a la vacuna. El objetivo de este trabajo fue determinar la relación entre alelos HLA específicos y la respuesta a la vacuna contra el VHB en pacientes que reciben hemodiálisis. Material y métodos: El estudio incluyó pacientes en hemodiálisis hospitalaria. Se recopilaron datos retrospectivamente del sistema electrónico de registros médicos sobre características demográficas, clínicas y de laboratorio, incluidos anticuerpos anti-HBs, anticuerpos contra la hepatitis C (anti-VHC), anti-VIH y alelos HLA específicos de clase I y II (HLA-A, HLA-B, HLA-DR). Se analizaron las frecuencias de los antígenos HLA clase I y II en pacientes que no respondían y en aquellos que sí lo hacían. Resultados: Los alelos HLA más comúnmente observados en pacientes fueron DQA1 * 01 (73,7%); DQA1 * 05 (57,9%); DQB1 * 03 (53,8%); DQB1 * 05 (38,5%), y DRB1 * 11 (37.3%), respectivamente. La frecuencia del alelo HLA-B40 fue significativamente mayor en los que no respondieron (p=0,02; OR = 6,25; IC 95% = 1,33-29,3). Se observó que los alelos HLA-DQA1*01 y HLA-DQB1*05 aparecían mayormente en los pacientes que respomdían (p=0,019; OR = 6,9; IC 95% = 1,40-33,91, y p=0,028; OR=10; IC 95% = 1,12- 88,91, respectivamente). Conclusión: Este es el primer estudio que conocemos que demuestra la asociación entre la respuesta de anticuerpos a HBsAg y a alelos HLA-B40, HLA-DQA1*01 y HLA-DQB1*05 en pacientes turcos en hemodiálisis.
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Las complicaciones secundarias a las infecciones por citomegalovirus (CMV) y virus de Epstein Barr (EBV) constituyen las principales causas de morbilidad y mortalidad por infecciones en los pacientes que reciben injertos de células progenitoras hematopoyéticas (CPH). La detección de anticuerpos específicos contra cada uno de estos virus en el periodo pretrasplante permite prevenir la primoinfección durante la inmunosupresión terapéutica.La investigación tuvo como objetivo determinar la seroprevalencia de anticuerpos anti-CMV y anti-EBV e identificar aquellos pacientes con riesgo de adquirir una infección primaria postrasplante.Se realizó la detección de anticuerpos IgM e IgG anti-CMV y anti-EBV por ELISA, a 110 pacientescon indicación de pruebas de histocompatibilidad para trasplante de CPH, entre enero del 2013 y enero del 2016, en el Departamento de Histocompatibilidad del Instituto de Hematología e Inmunología de La Habana.La seroprevalencia de anticuerpos anti-CMV en la población estudiada fue del 84,5 por ciento y anti-EBV, del 90,9 por ciento. Los menores de 9 años presentaron un porcentaje de positividad del 70,6 y 64,7 por ciento para IgG anti-CMV y EBV respectivamente, encontrándose un incremento de la seroprevalencia con la edad.La seroprevalenciade anticuerpos anti-CMV y anti-EBV en los pacientes en espera de trasplante de CPH en Cuba es semejante a otras poblaciones; lo que sugiere la necesidad evitar el contagio por transmisión a los casos seronegativos(AU)
Secondary complications due to infections caused by Cytomegalovirus (CMV) and Epstein Barr virus (EBV) are the major infectious causes of morbidity and mortality in recipients of hematopoietic stem cell (HSC) grafts. Detection of specific antibodies against each of those viruses in the pre-transplant period allows the prevention of the primary infection during the immune suppressive therapy.The aim of the investigation was to determine seroprevalence of antibodies against CMV and EBV and also to identify the patients in risk of a primary infection in the post-transplant period.The investigation was conducted between January 2013 and January 2016 by the Histocompatibility Department of Instiute of Hematology and Immunology. Antibodies IgM and IgG against CMV and EBV were tested by ELISA in 110 patients with the indication for histocompatibility testing for a HSC graft.Seroprevalence of antibodies against CMV in this population was 84.5 percent. and seroprevalence of antibodies against EBV was 90.9 percent. The 70.6 percent.of children less than 9 years old had positive IgG CMV antibodies and the 64.7 percent. of them had positive IgG EBV antibodies. An increase of seroprevalence with age was found. The seroprevalence of antibodies against CMV and EBV in patients waiting for a HSC transplant in Cuba is similar to the populations in other countries. This result suggests the need of avoiding the transmissiontoseronegative recipients(AU)
Subject(s)
Humans , Child, Preschool , Child , Enzyme-Linked Immunosorbent Assay , Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation/methods , Histocompatibility , Seroepidemiologic Studies , CubaABSTRACT
Recently developed computational methods allow the imputation of human leukocyte antigen (HLA) genes using intergenic single nucleotide polymorphism markers. To improve the imputation accuracy in HLA imputation, it is essential to increase the sample size and the diversity of alleles in the reference panel. Our software, MergeReference, helps achieve this goal by providing a streamlined pipeline for combining multiple reference panels into one.
Subject(s)
Humans , Alleles , HLA Antigens , Leukocytes , Major Histocompatibility Complex , Polymorphism, Single Nucleotide , Sample SizeABSTRACT
Epidemiological studies have shown that human leukocyte antigen (HLA) allelic polymorphisms are closely correlated to susceptibility to nasopharyngeal carcinoma (NPC), and in a previous study, we showed that HLA-B*46 and HLA-A*02-B*46 haplotypes were strongly associated with NPC susceptibility. In this retrospective study, we investigated the phenotype of the HLA-A and HLA-B alleles and haplotypes and correlated these data to the clinical and pathological parameters of NPC to understand the role of HLA alleles and haplotypes in NPC prognosis. The cohort comprised 117 NPC patients from a Han population in Xinjiang. The local recurrence-free survival (LRFS), distant metastasis- free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were analyzed. The 5-year DMFS of the HLA-A*02-B*46 haplotype carriers and non-carriers was 66.4% and 90.3%, respectively. In addition, age was found to be a prognostic factor for LRFS, DFS, and OS (P=0.032, 0.040, and 0.013, respectively). We found that the HLA-A*02-B*46 haplotype might be a prognostic marker in addition to the traditional TNM staging in patients with NPC.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Biomarkers, Tumor , Genetics , Carcinoma , Disease-Free Survival , HLA-A Antigens , Genetics , HLA-B Antigens , Genetics , Haplotypes , Nasopharyngeal Neoplasms , Genetics , Pathology , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Retrospective StudiesABSTRACT
Objective To investigate the correlation between human leukocyte antigens-A,-B,-DRB1 (HLA-A,-B,-DRB1) high resolution alleles and chronic renal failure (CRF) caused by immunoglobulin-a nephropathy (IgAN).Method The polymerase chain reaction-sequence-based typing (PCR-SBT) method was used to investigate the genotypes of HLA-A,-B and-DRB1 high-resolution alleles in 191 cases of CRF caused by IgAN (experimental group) and 503 healthy blood donors (control group).The alleles frequencies between two groups were compared and the association between CRF caused by IgAN and the polyrnorphism of HLA was analyzed.Result (1) There were 25 alleles at A locus,48 alleles at B locus and 32 alleles at DRB1 locus in experimental group.(2) The genetic frequency of HLAA * 2901 [Pc =0.033,OR =10.738,95％ CI (1.193,96.691)],HLA DRB1 * 1106 [Pc =0.0001,OR =0.969,95％ CI (0.944,0.994)],HLA-DRB1 * 1202[Pc =0.002,OR =1.859,95％ CI (1.259,2.745)],HLA-DRB1 * 1401 [Pc =0.021,OR =0.984,95％ CI (0.967,0.998)],HLA-DRB1 * 1602[Pc=0.015,OR=1.915,95％ CI (1.157,3.17)] in experimental group was higher than in control group (P＜0.05).Conclusion There is susceptibility association of HLA-A * 2901,HLA-DRB1 * 1106,HLA-DRE * 1202,HLA-DRB1 * 1401,HLA-DRB1 * 1602 with CRF caused by IgAN.It is concluded that there is a close genetic and immunological correlation between HLA alleles and the pathogenesis of CRF caused by IgAN.
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BACKGROUND: Human leukocyte antigen (HLA) is comprised of a highly polymorphic set of genes which determines the histocompatibility of organ transplantation. The present study was undertaken to identify HLA class I and class II allele, genotype and haplotype frequencies in renal transplant recipients and donors from West Central India. MATERIALS AND METHODS: HLA typing was carried out using Polymerase Chain Reaction-Sequence Specific Primer in 552 live related and unrelated renal transplant recipients and donors. RESULTS: The most frequent HLA class I and class II alleles and their frequencies in recipients were HLA-AFNx0101 (0.1685) and AFNx0102 (0.1649), HLA-BFNx0135 (0.1322), and HLA-DR beta 1 (DRB 1)FNx0115 (0.2192), whereas in donors, these were HLA-AFNx0102 (0.1848) and AFNx0101 (0.1667), HLA-BFNx0135 (0.1359), and HLA-DRB1FNx0115 (0.2409). The two-locus haplotype statistical analysis revealed HLA-AFNx0102-B61 as the most common haplotype with the frequency of 0.0487 and 0.0510 in recipients and donors, respectively. Further, among the three locus haplotypes HLA-AFNx0133-BFNx0144-DRB1FNx0107 and HLA-AFNx0102-BFNx0161-DRB1FNx0115 were the most common haplotypes with frequencies 0.0362 and 0.0326, respectively in recipients and 0.0236 and 0.0323, respectively in donors. Genotype frequency revealed a high prevalence of genotype HLA-AFNx0102/AFNx0124 in recipients (0.058) compared to donors (0.0109) whereas low prevalence of HLA-AFNx0101/AFNx0102 in recipients (0.0435) than in donors (0.0797). The phylogenetic and principal component analysis of HLA allele and haplotype frequency distribution revealed genetic similarities of various ethnic groups. Further, case control analysis provides preliminary evidence of association of HLA-A genotype (P < 0.05) with renal failure. CONCLUSION: This study will be helpful in suitable donor search besides providing valuable information for population genetics and HLA disease association analysis.
Subject(s)
Alleles , Ethnicity/genetics , Genotype , HLA Antigens/classification , HLA Antigens/genetics , Haplotypes , Humans , India , Kidney Transplantation/immunology , Polymorphism, GeneticABSTRACT
PURPOSE: To compare the frequency of conjunctival HLA-DR expression (a surrogate marker for inflammation) in eyes treated with topical prostaglandin analogues versus eyes treated with other topical antiglaucomatous drugs. METHODS: Patients diagnosed with primary open-angle glaucoma presenting indication for trabeculectomy were divided in groups according to the use or not of prostaglandin analogues. All subjects were treated with the maximum tolerated dose of antiglaucomatous drugs until the date of the surgery. At the beginning of the surgical procedure, a 5 x 5 mm biopsy of the bulbar conjunctiva was collected, incubated with monoclonal anti-HLA-DR antibody and processed for histological analysis. RESULTS: Of the 31 eyes included (31 patients), 25 were under topical prostaglandin analogues (Group 1) and six under other topical pharmacological agents (Group 2). Fourteen eyes of Group 1 (56%) and three of Group 2 (50 %) were positive for the inflammatory marker HLA-DR (P=1.0). The percentage of stained cells ranged from 15.49 to 48.09% (median: 27.61) in Group 1, and from 18.35 to 28 (median: 20.71) in Group 2, with no differences statistically significant (p=0.33). CONCLUSION: The use of prostaglandin analogues did not increase conjunctival expression of HLA-DR compared to other topical antiglaucomatous agents.
OBJETIVO: Comparar a frequência da expressão conjuntival de HLA-DR (marcador inflamatório) em olhos tratados com análogos de prostaglandinas de uso tópico com a frequência em olhos tratados com outros medicamentos. MÉTODOS: Pacientes com glaucoma primário de ângulo aberto apresentando indicação de trabeculectomia foram agrupados segundo o uso ou não de análogos de prostaglandinas. Todos os participantes foram tratados com medicação máxima tolerada até o momento da cirurgia. Ao início do procedimento cirúrgico, uma biópsia de 5 x 5 mm da conjuntiva bulbar foi coletada, incubada com anticorpo monoclonal anti-HLA-DR e processada para análise histológica RESULTADOS: Dentre os 31 olhos incluídos (31 pacientes), 25 estavam em uso de análogos de prostaglandinas (Grupo 1) e seis em uso de outros agentes antiglaucomatosos (Grupo 2). Quatorze olhos do Grupo 1 (56%) e três do Grupo 2 (50%) apresentaram positividade para o marcador HLA-DR (p=1,0). A porcentagem de células coradas variou de 15,49 a 48,09% (mediana: 27,61%) no Grupo 1 e de 18,35 a 28% (mediana: 20,71%) no Grupo 2, com diferenças não estatisticamente significativas (p=0,33). CONCLUSÃO: O uso de análogos de prostaglandinas não aumenta a expressão conjuntival de HLA-DR comparado com outros medicamentos tópicos para o tratamento de glaucoma.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Conjunctiva/drug effects , Conjunctivitis/chemically induced , Glaucoma/drug therapy , HLA-DR Antigens/analysis , Prostaglandins, Synthetic/adverse effects , Administration, Ophthalmic , Analysis of Variance , Biopsy , Biomarkers/analysis , Conjunctiva/pathology , Conjunctivitis/pathology , Glaucoma/surgery , Prostaglandins, Synthetic/therapeutic useABSTRACT
Objective In Caucasian populations, the tumor cells of Epstein Barr virus (EBV)-positive classical Hodgkin lymphoma (cHL) patients more frequently express HLA class Ⅰ and HLA class Ⅱ molecules compared to EBV-negative cHL patients. HLA expression (in relation to EBV) in Asian cHL patients has not been previously investigated. Methods 145 cHL patients with formalin-fixed, paraffin embedded tissue blocks available from Beijing, China were randomly selected. Hematoxylin & Eosin-stained slides were used to reclassify the histological subtypes according to the WHO classification. EBV status was determined by visualization of EBER in tumor cells using in situ hybridization. Membranous expression of HLA molecules was detected by immunohistochemistry using antibodies HC-10 (class Ⅰ heavy chain) and antiβ2-microglobulin for HLA class Ⅰ, and CR3/43 for HLA class Ⅱ. Results EBV (+) tumor cells were observed in 40 % (58/145) of the cHL patients. As expected, the percentage of EBV(+) cases was much higher in the mixed cellularity subtype (71%) than that in the nodular sclerosis subtype (16 %) (P ＜0.001). The expression of HLA class Ⅰ was observed in 79 % of the EBV (+) cHL cases and in 30 % of the EBV (-) cases (P ＜0.001). For HLA class Ⅱ, 52 % of EBV(+) cHL cases were positive, compared to 43 % in EBV(-) cases (P =0.277). Conclusion The results in China population were similar to that in the Caucasian population for HLA class Ⅰ, but not for HLA class Ⅱ.
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Donor-specific anti-human leukocyte antigen antibodies (DSA) following kidney transplantation predict the evolution of humoral rejection and reduced graft survival. Rapid, complete elimination of DSA during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. We report the case of a 39-year-old female who was admitted for increasing azotemia and diagnosed with AMR based on diffusely positive histological changes on C4d immunostaining. In this case, bortezomib reversed the histological changes and induced a reduction in DSA. Proteasome-inhibitor-based combination therapy is a potential means for rapid DSA elimination in antibody-mediated rejection in renal transplant recipients.
Subject(s)
Adult , Female , Humans , Antibodies , Azotemia , Boronic Acids , Complement C4b , Graft Survival , HLA Antigens , Kidney Transplantation , Leukocytes , Peptide Fragments , Proteasome Inhibitors , Pyrazines , Rejection, Psychology , Transplants , BortezomibABSTRACT
Donor-specific anti-human leukocyte antigen antibodies (DSA) following kidney transplantation predict the evolution of humoral rejection and reduced graft survival. Rapid, complete elimination of DSA during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. We report the case of a 39-year-old female who was admitted for increasing azotemia and diagnosed with AMR based on diffusely positive histological changes on C4d immunostaining. In this case, bortezomib reversed the histological changes and induced a reduction in DSA. Proteasome-inhibitor-based combination therapy is a potential means for rapid DSA elimination in antibody-mediated rejection in renal transplant recipients.
Subject(s)
Adult , Female , Humans , Antibodies , Azotemia , Boronic Acids , Complement C4b , Graft Survival , HLA Antigens , Kidney Transplantation , Leukocytes , Peptide Fragments , Proteasome Inhibitors , Pyrazines , Rejection, Psychology , Transplants , BortezomibABSTRACT
Objective To analyze the molecular genetic basis of novel allele HLA-B * 9534 and establish the allele group specific primer PCR method. Methods Genomic DNA was extracted from whole blood by commercial DNA extraction kit. The HLA-B exons 1 to 8 coding sequences of the proband were am-plified by PCR and the amplification product was purified with double enzymes digestion and both strands of exons 2, 3 and 4 were sequenced. The exon 2-4 amplification of the HLA-B * 9534 was performed with al-lele group specific primers PCR and the PCR product was directly sequenced for exon 2 to 4. Results The proband has two HLA-B alleles. The result was assigned for HLA-B * 1518 and B * 4601 combination with a mismatch in 593A/G heterozygote by DNA sequencing of exon 2 to 4 with loci primers. After separating the two alleles of the proband with allele group specific primers polymerase chain reaction method, HLA-B * 4601 and HLA-B * 9534 alleles were identified after sequencing. The HLA-B * 9534 is identical to HLA-B * 1518 except for one nucleotide substitutions in exon 3 at position 593 A→G, this results in amino acid substitution at cedon 174 from Asn to Ser. The sequences of the novel allele have been submitted to GenBank (EU046491) and the allele has been officially nominated by the WHO Nomenclature Committee. Conclusion Identification of a novel HLA-B * 9534 allele and allele group specific primer PCR for HLA-B * 9534 was re-liable.
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A 66-year-old male was admitted for increasing azotemia. He was diagnosed with chronic antibody- mediated rejection and had received a livingdonor renal transplant from his 32-year-old son prior to his admission. The peritubular capillaries of his kidney were diffusely positive on C4d immunostaining. It is known that there is an agreement between C4d staining and serological and histopathological data during rejection that is thought to have a humoral component. The role of alloantibodies in chronic renal allograft deterioration and the corresponding morphologic changes have been increasingly recognized during the recent years. However the treatment guidelines for chronic antibody-mediated rejection have not yet been established. Intravenous immunoglobulin (IVIG) has been shown to decrease the titers of anti-HLA antibodies in highly sensitized patients awaiting transplant. There are also numerous proposed mechanisms regarding how IVIG exerts its immunomodulatory action. As we have experienced chronic antibody-mediated rejection and how IVIG treatment improves renal function, we recognize that IVIG has the potential to be used for treating certain subgroups of chronic allograft nephropathy patients with positive C4d staining and anti-HLA antibodies.
Subject(s)
Adult , Aged , Humans , Male , Antibodies , Azotemia , Capillaries , Complement C4b , HLA Antigens , Immunoglobulins , Immunoglobulins, Intravenous , Isoantibodies , Kidney , Peptide Fragments , Rejection, Psychology , Transplantation, Homologous , TransplantsABSTRACT
BACKGROUND: Panel reactive antibody (PRA) test is used to determine whether a patient awaiting transplantation is previously sensitized. Tail analysis algorithm is widely used to identify antibody specificities, but it is very difficult to perform manually. METHODS: To develop a web-based program, PHP (5.1.2), Apache (2.0.55), and MySQL (5.0.22) were used. Tail analysis algorithm was applied to identify specificities, which analyzed statistically 2 x 2 tables representing reactivities to broad antigens, splits and cross reactive groups (CREG). Exploiting two CREG classifications of Rodey (R) and Takemoto (T), antibody specificities were identified by 3 methods (ABC, R-ABC, T-ABC) simultaneously. Performance of the system was evaluated using 159 samples that showed > or =6 PRA% by a lymphocytotoxicity assay. RESULTS: A web-based system that can identify HLA antibody specificities was implemented on www.koreanhla.com. Among 159 samples tested, antibody specificities were identified in 151 (95.0 %), but not in 8 samples with PRA >97%. Among the 151 samples, 110 showed broad or split specificities and 41 CREG specificities. CONCLUSIONS: We developed a web-based computer program for the identification of HLA antibody specificities. Accessible to everyone on the internet, this program should be of help in sharing PRA results among laboratories.
Subject(s)
Humans , Algorithms , Antibody Specificity/genetics , HLA Antigens/genetics , Histocompatibility Testing , Internet , SoftwareABSTRACT
Objective To detect the HLA DRB1*12 by use of a new genotyping method for HLA SYBR Green Ⅰ PCR. Methods 1 HLA DRB1*12 sample and 12 unknown clinical sample were collected. The typing of these samples were determined by PCR, which includes a fluorescence dye, SYBR GreenⅠ,and the sequence specific primer. SYBR GreenⅠcould bind to the dsDNA to exhibit fluorescence. The fluorescence enhancement depends on the accumulation of the amplified product. Results 3 of the 12 unknown sample was proved to be DRB1*12 by the analysis of the melting curve of the amplified products. After purification, the type of these products were confirmed DRB1*12 by DNA based sequencing. Conclusions The results of SYBR GreenⅠPCR demonstrate that it can be a new strategy for HLA typing because of its convenience and accuracy.