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Após identificação que o alelo DRB1*15 e que os polimorfismos TNFA– 308G/A e IL1B–511C/T podem conferir maior suscetibilidade ao desenvolvimento de anticorpos contra antígenos eritrocitários, verificamos em nossa casuística o número de pacientes que eram portadores de um ou mais destes fatores (alelos TNFA–308A, IL1B–511T e/ou DRB1*15). Esta análise mostrou que 121 dos 161 pacientes com AF (75%) analisados apresentavam pelo menos um dos fatores de

risco à aloimunização eritrocitária. Assim, com base em nossos resultados 75% dos pacientes com AF deveriam receber unidades de sangue compatíveis para um maior número de antígenos eritrocitários, incluindo variantes RH como uma forma de profilaxia da aloimunização eritrocitária.

A análise destes polimorfismos como fatores de risco a aloimunização eritrocitária em pacientes portadores de AF pode contribuir futuramente na seleção dos pacientes respondedores que devem receber concentrado de hemácias com compatibilidade genética estendida, com o objetivo de redução da aloimunização eritrocitária e dos efeitos adversos às transfusões.

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6 CONCLUSÃO

Com base nos resultados obtidos podemos concluir que:

- A frequência de aloanticorpos eritrocitários em pacientes portadores de AF foi 41,6%.

- A aloimunização eritrocitária não foi associada com o número de transfusões, sexo ou idade.

- A frequência de autoanticorpos em pacientes aloimunizados foi de 55,22%.

- Não foi observado diferença significativa entre os fenótipos eritrocitários dos pacientes aloimunizados e não aloimunizados.

-O fenótipo eritrocitário mais frequente entre os pacientes foi C– E–, K–, Fy(a–), Jk(b-), S–, Di(a-).

- A caracterização molecular de variantes RHD e RHCE contribuiu para a diferenciação de auto e aloanticorpos Rh.

- Os alelos RHD variantes mais frequentemente encontrados entre os pacientes com anticorpos Rh foram RHD*DAR, RHD*fraco parcial 4.0, RHD*DIIIa e RHD*DAU0. Os alelos RHCE variantes mais frequentes foram RHCE*ceS, RHCE*ce48C, RHCE*ce733G, RHCE*ceAR e RHCE*ceTI.

- Aloimunização Rh associada com a presença de alelos RH variantes é alta e os anticorpos podem ser clinicamente significantes.

- O alelo A do SNP TNFA–308G/A, o alelo T do SNP IL1B–511T/C e os genótipos TNFA–308GA e IL1B–511TT e CT podem conferir susceptibilidade a aloimunização eritrocitária em pacientes portadores de AF.

- Os polimorfismos IL10–1082G/C, IL10–819T/C, IL10–592C/A, IL17A– 197A/G, IL17F 7488A/G, IL6–174C/T, IL4-590C/T e IL4 íntron 3 VNTR não mostraram associação com a aloimunização eritrocitária em pacientes com AF de nossa casuística.

- A molécula HLA-DRB1*15 e o haplótipo HLA-DRB1*15/TNFA–308G podem conferir suscetibilidade a aloimunização Rh em pacientes com AF politransfundidos.

- A detecção de polimorfismos em genes de citocinas pró-inflamatórias e alelos HLA podem ajudar a prever pacientes respondedores e não-respondedores.

- Em nosso trabalho, 75% dos pacientes com AF deveriam receber unidades de sangue compatíveis para um maior número de antígenos eritrocitários, incluindo variantes RH como uma forma de profilaxia da aloimunização eritrocitária.

- Os resultados obtidos podem contribuir futuramente na seleção de unidades de sangue compatíveis para pacientes com AF em risco de aloimunização.

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