Determination of an unrelated donor pool size for human leukocyte antigen-matched platelets in Brazil

ABSTRACT Background: Successful transfusion of platelet refractory patients is a challenge. Many potential donors are needed to sustain human leukocyte antigen matched-platelet transfusion programs because of the different types of antigens and the constant needs of these patients. For a highly mixed population such as the Brazilian population, the pool size required to provide adequate platelet support is unknown. Methods: A mathematical model was created to estimate the appropriate size of an unrelated donor pool to provide human leukocyte antigen-compatible platelet support for a Brazilian population. A group of 154 hematologic human leukocyte antigen-typed patients was used as the potential patient population and a database of 65,500 human leukocyte antigen-typed bone marrow registered donors was used as the donor population. Platelet compatibility was based on the grading system of Duquesnoy. Results: Using the mathematical model, a pool containing 31,940, 1710 and 321 donors would be necessary to match more than 80% of the patients with at least five completely compatible (no cross-reactive group), partial compatible (one cross-reactive group) or less compatible (two cross-reactive group) donors, respectively. Conclusion: The phenotypic diversity of the Brazilian population has probably made it more difficulty to find completely compatible donors. However, this heterogeneity seems to have facilitated finding donors when cross-reactive groups are accepted as proposed by the grading system of Duquesnoy. The results of this study may help to establish unrelated human leukocyte antigen-compatible platelet transfusions, a procedure not routinely performed in most Brazilian transfusion services.

Nomenclatura dos fatores do sistema HLA / Nomenclature for factors of the HLA system

The Nomenclature Committee for Factors of the HLA System of the World Health Organization standardizes the nomenclature of the HLA system and meets regularly during the International Histocompatibility Workshops. During the 15th International Histocompatibility Workshop in Buzios (RJ), Brazil, in September 2008, there was a meeting of the nomenclature committee when new rules were established, whichwere implemented in April 2010.

O Comitê de Nomenclatura dos Fatores do Sistema HLA da Organização Mundial da Saúde normatiza a nomenclatura do sistema HLA e se reúne regularmente durante os Workshops Internacionais de Histocompatibilidade. Durante o 15o Workshop Internacional de Histocompatibilidade, em Búzios (RJ), em Setembro de 2008, houve a reunião do comitê de nomenclatura, quando novas regras foram estabelecidas, sendo implantadas em Abril de 2010.

Diagnosis and treatment of acute antibody-mediated rejection in renal transplant: the role of C4d and donor-specific antibody identification / Diagnóstico e tratamento da rejeição aguda mediada por anticorpo no transplante renal: papel do C4d e da pesquisa de anticorpo específico contra o doador

Objective: To evaluate the incidence of antibody-mediated rejection after the C4d and donor specific antibody detection was provided by Luminex in renal transplantation biopsies; to compare acute antibody-mediated rejection characteristics as related to acute cellular rejection; to evaluate the impact on the incidence of acute antibody mediated rejection after the utilization of cross match test by flux cytometry and the detection of pre-transplantation donor specific antibody in patients with previous history of exposition to alloantigens. Methods: One hundred twenty-four renal transplanted patients were evaluated through the detection of C4d in early biopsies of those presenting graft dysfunction and the detection of antibody against donor when C4d was positive. The acute antibody mediated rejection was treated by plasmapheresis and intravenous immunoglobulin. Results: The incidence of acute rejection was 18.8%, being the acute cellular rejection 14.9% and acute antibody mediated rejection 6.6%. When both were compared, the acute antibody-mediated rejection were earlier than the acute cellular rejection (12.5 versus 59.9 days, p = NS), being more frequent in female patients (75 versus 29%, p = 0.05), with deceased donors (75 versus 33%, p = 0.09), with higher dialysis time (87.7 versus 47.4, p = 0.03), greater number of transfusion episodes (4.6 versus 1.4, p = 0.02), greater panel reaction activity (28.0 versus 4.8, p = 0.03) and more frequently in re-transplanted patients (50 versus 5.6%, p = 0.02). Delayed graft function was more frequent in antibody mediated rejection (100 versus 50%, p = 0.02). All patients with acute cellular rejection reversed graft function after treatment, with 100% graft survival after one year. Among patients with acute antibody-mediated rejection, the treatment with plasmapheresis and immunoglobulin was efficient in reducing the titers of donor specific antibody (2605 versus 202 mfi, p < 0.001), but 3/8 of patients evolved to graft loss, making graft survival of 62.5% (p < 0.001). Conclusions: The routine use of detecting C4d and donor specific antibody increased the incidence of acute rejection. Acute antibody-mediated rejection presented clinical profile and therapeutic response different from acute cellular rejection, identifying a worse prognosis as well as therapeutic success.

Objetivo: Avaliar a incidência da rejeição mediada por anticorpo depois de instituída a pesquisa de C4d em biópsias de rim transplantado e pesquisa de anticorpo específico de doador pelo Luminex; comparar as características da rejeição aguda mediada por anticorpo em relação à rejeição aguda celular; avaliar o impacto na incidência de rejeição aguda mediada por anticorpo após utilizar a prova cruzada por citometria de fluxo e pesquisa de anticorpo específico de doador pré-transplante em pacientes com histórico de exposição prévia à aloantígenos. Métodos: Foram avaliados 124 pacientes transplantados renais, com pesquisa de C4d em biópsias precoces em pacientes com disfunção do enxerto e pesquisa de anticorpo contra o doador quando o C4d foi positivo. A rejeição aguda mediada por anticorpo foi tratada com plasmaferese e imunoglobulina intravenosa. Resultados: Foi encontrada uma incidência de rejeição aguda de 18,8%, com frequência de episódios de rejeição aguda celular de 14,9% e de rejeição aguda mediada por anticorpo de 6.6%. Quando comparados com rejeição aguda celular, os episódios de rejeição aguda mediada por anticorpo foram mais precoces (12,5 versus 59,9 dias, p = NS), sendo mais frequentes em pacientes femininas (75% versus 29%, p = 0,05), com doadores falecidos (75% versus 33%, p = 0.09), com maior tempo de diálise (87,7 versus 47,4, p = 0,03), maior número de transfusões (4,6 versus 1,4, p = 0,02), maior atividade contra painel (28,0 versus 4,8, p = 0,03) e mais frequentemente retransplantados (50 versus 5,6%, p = 0,02). Função retardada do enxerto foi mais frequente nos pacientes com rejeição aguda mediada por anticorpo (100 versus 50%, p = 0,02). Todos os pacientes com rejeição aguda celular reverteram a função do enxerto após o tratamento, com sobrevida do enxerto, em um ano, de 100%. Entre os pacientes com rejeição aguda mediada por anticorpo, o tratamento com plasmaferese e imunoglobulina foi eficiente em reduzir os títulos de anticorpo específico de doador (2.605 versus 202 mpi, p < 0,001), mas 3/8 pacientes evoluíram para perda do enxerto, conferindo sobrevida do enxerto de 62,5% (p < 0,001). Conclusões: O uso rotineiro da pesquisa de C4d e anticorpo doador específico aumentou a incidência de rejeição aguda. A rejeição aguda mediada por anticorpo apresentou perfil clínico e resposta terapêutica diferentes da rejeição aguda celular, conferindo-lhe pior prognóstico e pior resposta terapêutica.

Utilização da técnica de PCR para monitoramento molecular de quimerismo pós-transplantes / Using PRC for molecular monitoring of p´post transpalntation chimerism

O monitoramento pós-transplante de órgãos sólidos e medula óssea tornou-se uma ferramenta imprescindível para aumentar a sobrevida dos enxertos, sendo o termo quimerismo utilizado paradescrever a presença de células do doador nos pacientes receptores de transplantes. O presente artigo descreve as diversas aplicações e avanços nas técnicas que podem ser utilizadas para a detecção e monitoramento quantitativo do quimerismo póstransplantes,em especial a metodologia de PCR utilizando oligonucleotídeos fluorescentes e seqüenciadores automáticos para amplificação e detecção de marcadores conhecidos como microssatélites, ou STRs.