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Aloimmunity against HLA class I antigens in patients with myelodysplastic syndrome and aplastic anemia / Aloimuniodade contra os antÃgenos HLA de classe I em pacientes portadores das sÃndromes mielodisplÃsticas e de anemia aplÃsticaDaisy Maria Meireles Arruda 22 July 2005 (has links)
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Myelodysplastic syndrome (MDS) and aplastic anemia (AA) are two of the hematological disorders which present peripheral cytopenias, with extensive clinical manifestations that vary from slight anemia to severe pancytopenia; the latter requiring continuous transfusional reposition of red cell (RC) and platelet concentrates (PC), which can induce aloimunization in patients. Such patients can develop a post-transfusional refractory state, rendering further transfusions unviable. The objective of the present study was to investigate the incidence of anti-HLA antibodies in politransfused patients, and correlate the aloimmunity levels to the clinical profiles of MDS and AA patients. A total of 110 politransfused patients (70 with MDS, and 40 with AA) have been included in the study, with the MDS patients being subclassified into four clinical diagnostic categories: refractory anemia (RA), ringed-sideroblastic refractory anemia (RSRA), refractory anemia with excess blasts (RAEB) and refractory anemia with excess blasts in transformation (RAEB-t). Blood serum samples from these patients were treated with dithiothreitol for the detection of anti-HLA class I antibodies, using the complement-dependent cytotoxicity test (CDC), in a panel of lymphocytes constituted on the basis of the frequency of HLA antigens in our population (PRA). The results showed that a larger number of AA patients were aloimmunized than MDS patients (45% v 28.6%), with the aloreactivity being higher in AA patients who received higher mean transfusions of PC, than in MDS patients who received higher average number of EC transfusions. The degree of aloimmunization was different in the two disorders, and was generally related to: the number of transfusions received, the application of un-deleukocytised PC and EC, and the type of immunosuppressant drugs used in treatment [Cyclosporin (CsA) and/or antiglobulin (ALG) therapy significantly reduced aloimmunization, but corticoids alone were not sufficient]. The highest degree of aloimmunity (Grade 4) was observed only in MDS females, particularly in those who had multiple births. Persistent IgG was also associated with Grade 4 aloimmunity. These results reveal that significant numbers of MDS and AA patients, if politransfused with un-deleukocytised PC and EC and un-treated with immunosuppressants CsA and/or ALG, can develop anti-HLA antibodies and become refractory to further transfusions. Such aloimmunized patients can also become potentially unsuited to receive bone marrow transplants from HLA-matched donors. / As SÃndromes MielodisplÃsticas e Anemia AplÃstica sÃo desordens hematolÃgicas que apresentam citopenias perifÃricas, com desenvolvimento de caracterÃsticas clÃnicas extensas, com manifestaÃÃes clÃnicas variÃveis que vÃo desde uma leve anemia atà uma pancitopenia severa, necessitando, nos Ãltimos casos, de reposiÃÃo transfusional contÃnua de concentrados de hemÃcias (CH) e de plaquetas (CP), tornando-os alvos à aloimunizaÃÃo pÃs-transfusional e desenvolvimento do estado de refratariedade Ãs transfusÃes. Este estudo objetivou determinar a incidÃncia de anticorpos anti-HLA de classe I em pacientes politransfundidos e correlacionar a aloimunidade ao perfil clÃnico dos pacientes de SMD e AA. 110 pacientes foram incluÃdos nesta pesquisa (70 portadores das SMD e 40 de AA), com os portadores das SMD classificados em quatro sub-grupos clÃnicos: anemia refratÃria (AR), anemia refratÃria sideroblÃstica em anel (ARSA), anemia refratÃria com excesso de blastos (AREB) e anemia refratÃria com excesso de blastos em transformaÃÃo (AREB-t). Soros dos pacientes foram tratados com Dithiothreitol (DTT) para a pesquisa de Acs contra os Ag HLA de classe I, usando a tÃcnica de âcitotoxicidade dependente do complementoâ (CDC), no painel de linfÃcitos baseado na frequÃncia dos Ags HLA da nossa populaÃÃo (PRA). Os resultados demonstraram que os pacientes portadores das SMD desenvolveram um menor grau de aloimunizaÃÃo (28,6%), que os pacientes de AA (45%). A alorreatividade foi mais freqÃente nos portadores de AA que tinham recebido maiores mÃdias transfusionais de CP, em relaÃÃo aos pacientes de SMD que receberam maior nÃmero de transfusÃes com CH. O grau de alorreatividade se manifestou diferente nestas duas doenÃas e, de forma geral, se relacionou com: o maior nÃmero mÃdio de transfusÃes, a aplicaÃÃo de preparaÃÃes nÃo desleucotizadas de CH e CP e o uso de imunossupressores (ciclosporina e/ou soros anti-leucocitÃrios). Somente o uso de corticÃide nÃo foi suficiente para reduzir a aloimunizaÃÃo. O mais alto grau de alorreatividade (PadrÃo 4) nas SMD foi evidenciado somente em mulheres, principalmente nas multÃparas. IgG persistente esteve mais presente no PadrÃo 4. Estes dados revelam que alguns pacientes das SMD e AA podem desenvolver anticorpos anti-HLA, se forem politransfundidos com hemoconcentrados nÃo desleucotizados e sem o tratamento com os imunossupressores CsA e/ou GAL. Tal alorreatividade poderà tornar o paciente refratÃrio Ãs futuras transfusÃes e dificultar, em princÃpio, recebimento do transplante de medula Ãssea de doadores HLA compatÃveis.
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