Identification of a rare platelet-specific antigen HPA-10bw allele among ethnic Han Chinese population in Shandong / 中华医学遗传学杂志

OBJECTIVE@#To study the polymorphism of human platelet antigen (HPA) system 10 among ethnic Han Chinese from Shandong, China so as to supplement the data of platelet donor bank in the region.@*METHODS@#Peripheral blood samples of platelet donors from the region were genotyped for HPA-10 alleles by PCR-sequence specific primer (PCR-SSP) and direct sequencing.@*RESULTS@#Among 1401 donors, a rare heterozygote carrier of HPA-10w (a+b+) was identified, which gave an allelic frequency of approximately 0.035%.@*CONCLUSION@#The detection of rare HPA-10bw antigen allele among ethnic Han Chinese from Shandong is useful for the diagnosis and prevention of neonatal alloimmune thrombocytopenia and post-transfusion purpura in the region.

Platelet HPA Typing of Platelet Donors in Zhangjiakou Area / 中国实验血液学杂志

OBJECTIVE@#To analyze the polymorphism of the HPA1-5,15 system of the donors in Zhangjiakou area.@*METHODS@#DNA was extracted from the blood samples of the donors, PCR- SSP method was used to divide HPA1-6, 15 genotype. The gene frequency and genotype frequency were calculated, compared with the difference and regiahal specificity of the populations in our country and foregiens was compared other populations.@*RESULTS@#The gene expression in the HPA-1, HPA-2 and HPA-4 systems were all homozygous aa, and the donors who expressed homozygous bb was not exessed. Among them, one heterozygous ab expression was found in both HPA-1 and HPA-4 systems (1%), and 14 cases of heterozygous ab expression were found in HPA-2 system (14%). The gene expression in the HPA-5 system was mainly homozygous aa (98%), and a very few expressed homozygous bb (2%) was found. The degree of heterozygosity of gene expression in the HPA-3 and HPA-15 systems was relatively high. The proprotion of the expression of aa, ab and bb in the HPA-3 system was respectively 46%, 40% and 14%, the proprotion of the expression of aa, ab and bb in the HPA-15 system was respectively 21%, 64% and 15%.@*CONCLUSION@#The gene frequency of platelet-specific antigen HPA1-5,15 system in zhangjiakou region shows local characteristics. The heterozygosity degree of gene expression in the HPA-3 and HPA-15 systems are both high, suggesting that they are more likely to result in alloimmunization and ineffective platelet transfusion, which should be pays attention to.

Analysis on Polymorphism of Platelet Antigen Gene in Shandong Han Population / 中国实验血液学杂志

OBJECTIVE@#To study the Polymorphism of the human platelet antigen(HPA) gene 1-17 and human leukocyte antigen(HLA) gene-A and B locus in Shandong Han population.@*METHODS@#A total of 962 samples from routine voluntary platelet donors were genotyped for HPA1-17 system and HLA-A site, B by PCR-SSP and PCR-SSOP respectively．Gene frequencies were calculated by counting. HPA1-17 and HLA genotype combinations were analyzed by Arelequin 3.5.@*RESULTS@#The gene frequencies of HPA-la, -1b, HPA-2a, -2b, HPA-3a, -3b, HPA-4a, -4b, HPA-5a, -5b, HPA-6a, -6b, HPA-15a, -15b were 0.9918, 0.0082, 0.9419, 0.0592, 0.5841, 0.4174, 0.9969, 0.0031, 0.9892, 0.0108, 0.9835, 0.0175,0.5488 and 0.4512, respectively． The most common HPA genotype combination was HPA-(1, 2, 4, 5, 6, 7-14, 16, 17) aa-3ab-15ab (0.2048). Moreover, HLA-A*2(0.3094) and HLA-B*13(0.1513) showed the highest frequency in their respective locus. The most common HLA genotype combination was HLA-A*2-B*13(0.1397) .@*CONCLUSION@#Distributions of HPA and HLA show high polymorphism in Shandong Han population. The ethnic and territorial difference of HPA distribution is also confirmed. It is imperative to establish local genetic database of volunteer platelet donors.

Human platelet antigen-3 polymorphism as a risk factor for rheumatological manifestations in hepatitis C

Abstract INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.

Introducción del genotipaje molecular de los antigenos plaquetarios / Introduction of molecular genotypingof plateles antigens

Introducción: Los antígenos plaquetarios humanos (HPA) se expresan en 6 glucoproteínas plaquetarias diferentes. Se ha descrito que estos antígenos pueden estimular la producción de aloanticuerpos una vez expuestos a plaquetas humanas con diferentes HPA, lo que provoca complicaciones clínicas como la trombocitopenia neonatal aloinmune y la púrpura postransfusional. Métodos: Se realizó el estudio a 11 muestras de pacientes en espera de trasplante renal de genotipo de los antígenos HPA-1,2,3 a/b mediante PCR multiplex, mientras que para el estudio de genotipo de los antígenos HPA-5a/b se utilizó la técnica de PCR con secuencia específica de primer. Los productos de ADN amplificados fueron visualizados mediante electroforesis en gel de agarosa y electroforesis capilar. Resultados: El análisis de los fragmentos de ADN amplificados revelaron resultados similares por ambos métodos. Para los antígenos HPA-1,-2, el 63 por ciento de las muestras fueron homocigóticas para el fenotipo (a) mientras que se observó heterocigocidad en todos los casos para el genotipo HPA-3. En el sistema HPA-5, el 54 por ciento fueron homocigóticas para el fenotipo (a) y el 46 por ciento, heterocigóticas. Para el genotipo del HPA-15, el 4 por ciento fueron homocigóticas para el fenotipo (b) mientras que el 96 por ciento resultaron ser heterocigóticas. Conclusiones: Estos resultados muestran similitudes para los genotipos HPA 1, 2,3 a/b, HPA 5a/b y HPA15 a/brespecto a lo planteado en la literatura(AU)

Introduction: Human platelet antigens (HPA) are expressed in 6 different platelet glycoproteins. It has been described that these antigens can stimulate the production of alloantibodies once exposed to human platelets with different HPA, which causes clinical complications such as neonatal alloimmune thrombocytopenia and postransfusional purpura. Methods: The study was performed on 11 samples of patients awaiting kidney transplantation of genotype of the HPA-1,2,3 a/b antigens by multiplex PCR, while for the genotype study of the HPA-5a/b antigens was used the PCR technique with primer-specificsequence. The amplified DNA products were visualized by agarose gel electrophoresis and by capillary electrophoresis. Results: The analysis of DNA fragments amplified by agarose electrophoresis and capillary electrophoresis revealed similar results in both methods. For the HPA-1, -2 antigens, 63 percent of the samples were homozygous for phenotype (a) while heterozygosity was observed in all cases for the HPA-3 genotype. In the HPA-5 system, 54 percent were homozygous for the phenotype (a) and 46 percent were heterozygous. For the genotype of HPA-15, 4 percent were homozygous for phenotype (b) while 96 percent proved heterozygous. Conclusions: These results show similarities for the genotypes HPA 1, 2.3 a/b, HPA 5a/b and HPA15 a/bwith respect to report in literature(AU)

Allele and haplotype frequencies of human platelet and leukocyte antigens in platelet donors / Frequência alélica e haplotípica dos antígenos plaquetários e leucocitários humanos em doadores de plaquetas

ABSTRACT Objective To described the allele and haplotype frequencies of human leukocyte antigen genes at the -A, -B loci and human platelet antigen genes for human platelet antigen systems 1 to 9, 11 and 15 in blood. Methods We included 867 healthy unrelated volunteer donors who donated platelets between January 2011 and December 2014. Microarray genotyping was performed using a BeadChip microarray. Medium resolution typing of the human leukocyte antigen at loci A and B was carried out using sequence-specific oligonucleotide probe hybridization. We used multivariate analysis and our human leukocyte antigen population was compared to data from the United States national bone marrow donor program. Human platelet antigen results were compared to a literature review and data from around the world. Results Our human leukocyte antigen haplotype results were more similar to those of hispanics, followed by caucasians. Likewise, our human platelet antigen sample is more similar to those of Argentina, Rio Grande do Sul and Italy. Conclusion This was the first article that discusses human platelet antigen and human leukocyte antigen data together. Rare genotypes or antibody associations can make patient management difficult. A blood bank with genotyped donors allows for optimal transfusion and can contribute to better results. Our information can serve as basis for a database of platelet antigen polymorphisms.

RESUMO Objetivo Descrever as frequências alélicas e haplotípicas de genes dos antígenos leucocitários humanos nos loci -A,- B e dos antígenos plaquetários humanos para os sistemas HPA-1 a 9, 11 e 15. Métodos Foram incluídos 867 doadores voluntários, saudáveis, não relacionados, que doaram plaquetas por aférese entre janeiro de 2011 e dezembro de 2014. A genotipagem foi realizada usando microarray BeadChip. A tipificação de resolução intermediária dos antígenos leucocitários humanos loci A e B foi realizada por meio de hibridização com sonda para oligonucleotídeos por sequência específica. Utilizamos análises multivariadas e o antígeno leucocitário humano de nossa população foi comparado com a do programa nacional de doadores de medula óssea norte-americano. Já os resultados dos antígenos plaquetários humanos foram comparados à revisão da literatura e a dados de populações de outros países. Resultados Os resultados do haplótipo de antígenos leucocitários humanos são mais parecidos com os dos hispânicos, seguidos dos caucasianos. Igualmente, a amostra de antígenos plaquetários humanos foi mais semelhante às da Argentina, do Rio Grande do Sul e da Itália. Conclusão Este foi o primeiro artigo a discutir antígenos plaquetários e leucocitários humanos simultaneamente. Genótipos raros ou associações de anticorpos podem dificultar o manejo clínico do paciente. Um banco de sangue com doadores genotipados permite um melhor resultado e transfusão possíveis. Estas informações podem servir de base para um banco de dados sobre polimorfismos de antígenos plaquetários.

HPA-1a/1b could be considered a molecular predictor of poor prognosis in chronic hepatitis C

Abstract INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.

The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients.

Successful management of neonatal alloimmune thrombocytopenia in the second pregnancy: a case report / Sucesso no manejo da trombocitopenia aloimune neonatal na segunda gestação: relato de caso

Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother produces antibodies against fetal platelet antigens inherited from the father; it is still an underdiagnosed disease. This disease is considered the platelet counterpart of the RhD hemolytic disease of the fetus and newborn, yet in neonatal alloimmune thrombocytopenia the first child is affected with fetal and/or neonatal thrombocytopenia. There is a significant risk of intracranial hemorrhage and severe neurological impairment, with a tendency for earlier and more severe thrombocytopenia in subsequent pregnancies. This article reports a case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and discusses diagnosis, management and the clinical importance of this disease.

A púrpura trombocitopênica neonatal aloimune é uma doença grave, na qual a mãe produz anticorpos contra antígenos plaquetários fetais herdados do pai, e é ainda subdiagnosticada na prática clínica. É considerada o equivalente plaquetário da doença hemolítica do recém-nascido, com a diferença que o primeiro filho é afetado, apresentando trombocitopenia fetal e/ou neonatal. Há risco significativo de hemorragia intracraniana e sequelas neurológicas graves, com tendência a trombocitopenia mais grave e mais precoce nas gestações subsequentes. Este artigo relata um caso de trombocitopenia aloimune neonatal na segunda gestação afetada e discute diagnóstico, manejo e importância clínica dessa doença na prática clínica.

role of human platelet antigen 1 polymorphism in development of coronary artery stenosis in Iranian population

Aggregation is the final step in activation of platelets and is mediated by presentation of GPIIb/IIIa receptors on the platelet membrane that bands to fibrinogen and von Willebrand's factor. There are common mutations in GPIII structure that can change the behavior of the molecule and may change the pattern of interaction between platelets and injured endothelium, thus they can have prognostic impact in coronary artery disease [CAD] and acute coronary syndrome. In some large trials, persons homozygous for the PIA2 allele had a greater chance of coronary stenosis and myocardial infarction [MI] than heterozygotes or non-carriers, but other studies did not confirm this association. This is the first study of PIA polymorphism in Iran and is aimed to find a possible association of this mutation and CAD in the Iranian population. In this case-control study, we chose 200 patients who underwent diagnostic coronary angiography between 2005 and 2006 in Hamedan, Iran. In these patients HPIa genotype determination was done using PCR method. We found no significant association of coronary artery stenosis and PIA2A2 or P1A1A2 genotypes in our patients, p value > 0.05. However, there was a significant association between possession of P1A2 allele and occurrence of CAD in patients more than 50 years of age, p value 0.045. Variations in P1A phenotype do not seem to have an association with ischemic heart disease, but the P1A2 allele may have a role in the development of atherosclerosis and MI in persons more than 50 years of age

A case report of neonatal alloimmune thrombocytopenic purpura: the importance of correct diagnosis for future pregnancies

CONTEXTO: Púrpura trombocitopênica neonatal aloimune (PTNA) é uma doença neonatal caracterizada por aloimunização materna contra as plaquetas fetais, que apresentam antígenos herdados do pai. Podem ocorrer hemorragias cerebrais, levando à morte ou a anomalias neurológicas permanentes. RELATO DE CASO: Mulher saudável, de 30 anos, deu à luz, por parto cesariano na 36ª semana de gestação, seu primeiro filho. Com 10 horas de vida, o recém-nascido apresentou petéquias e contagem de 8 x 103 plaquetas/µl no sangue periférico; foi medicado com imunoglobulina e recebeu alta após 18 dias de internação, com 100 x 103 plaquetas/µl. A causa da trombocitopenia não foi elucidada na época. Um ano depois, a criança morreu de neuroblastoma. Como os pais desejavam outro filho, foram encaminhados para investigação da trombocitopenia. Genotipagem plaquetária e pesquisa de anticorpos antiplaquetários foram realizadas, mostrando total falta de concordância entre os sistemas HPA-1 do pai (HPA-1a1a) e da mãe (HPA-1b1b) e anticorpos anti-HPA-1a no soro da mãe. Concluímos que o primeiro bebê nasceu com PTNA. Por isso, na segunda gravidez, a mãe foi tratada com diversas infusões de imunoglobulina intravenosa. Foi realizado cuidadoso monitoramento por ultra-som, com resultados normais para mãe e feto durante a gravidez. O segundo bebê nasceu por cesárea às 39 semanas, apresentando 92 x 103 plaquetas/µl seis horas após o nascimento. As plaquetas do recém-nascido foram genotipadas como HPA-1a1b e o soro da mãe novamente mostrou anticorpos anti-HPA-1a. Não houve hemorragia. A terapia de infusão de imunoglobulina foi efetiva na prevenção da PTNA no segundo filho.

Estudio del polimorfismo leu33/pro33 del receptor glicoproteico plaquetario IIIa (PIA) y su relación con la reestenosis postangioplastia coronaria con stent en una población argentina / Study of the relationship between the leu33/pro33 polymorphism of platelet glycoprotein receptor IIIa and post-coronary angioplasty in-stent restenosis in an argentinian population

Introducción: En pacientes con el polimorfismo del receptor plaquetario IIIa (PIA2), más en homocigotos PIA2/A2, se observó un porcentaje mayor de reestenosis postangioplastia coronaria con stent que en los pacientes PIA1/A1 o normales. Objetivo: Determinar la presencia del alelo polimórfico PIA2 en pacientes con reestenosis postangioplastia con stent en una población argentina; evaluar porcentaje de PIA2/A2 entre los reestenosadores y determinar la penetrancia del alelo polimórfico PIA2 en una población de nuestro país sin antecedentes coronarios. Métodos: Se evaluaron 45 pacientes, que integraron tres poblaciones. Díez sin antecedentes coronarios (9 hombres, 30 ± 5 años). Dieciseis pacientes con angioplastia (13 hombres, 62 ± 11 años) con control angiográfico a los 7 ± 1 mes que no evidenció reestenosis y 19 con reestenosis postangioplastia (16 hombres, 60 ± 12 años). Se consideró reestenosis una lesión mayor del 50 por ciento en el reestudio. Se realizó la reacción en cadena de la polimerasa en busca de la presencia del alelo PIA2. Se utilizó la prueba de Fischer para comparaciones. Resultados: De los 19 pacientes reestenosadores, 9 presentaron el alelo A2 (47 por ciento); de los 16 pacientes no reestenosadores presentaron el alelo A2 sólo el 13 por ciento (p < 0,04). De los 10 pacientes sin antecedentes se detectó un solo A2 (10 por ciento). Sólo 2 pacientes eran homocigotos A2/A2 y se encontraron en el grupo reestenosador. Conclusión: La presencia del alelo A2 (PIA1/A2 o PIA2/A2) fue significativamente mayor en los pacientes con reestenosis, lo cual podría ser un predictor de reestenosis postangioplastia con stent y su detección previa podría tener implicaciones terapéuticas.

Genotyping of human platelet antigens in ethnic Northeastern Thais by the polymerase chain reaction-sequence specific primer technique.

Human platelet antigens (HPA) are important in neonatal alloimmune thrombocytopenia (NAITP), post-transfusion purpura (PTP), refractoriness to platelet transfusion therapy and population genetics. The distribution of HPA in a Northeast Thai population was studied. 300 healthy, unrelated, and ethnic Northeastern Thais were randomly selected. Using the polymerase chain reaction-sequence specific primer technique (PCR-SSP), the frequency of HPA-1, -2, -3, -4, -5 and -6 were determined. The phenotype frequencies were 100 per cent for HPA-1a, 4a, 5a, and 6a. For HPA-1b, 2a, 2b, 3a, 3b, 5b and 6b, the frequencies were 5.7, 99.7, 12.3, 78.0, 71.3, 7.3 and 3.0 per cent, respectively. The HPA-4b was not found. The HPA frequencies in our subjects were quite similar to other Asian populations but were different from Caucasians. The distribution of HPA genotypes encountered in our study indicate that HPA-1a, -4a, -4b, -5a and -6a will not be involved in NAITP, PTP and refractoriness to platelet transfusion therapy in Northeastern Thais. Moreover, HPA-1b, -2a, -2b, -3a, -3b, -5b and -6b may induce alloantibodies in these patients.