Correlação clinica e imunologica do microquimerismo do sangue periferico e impacto dos fatores imunogeneticos em pacientes brasileiros apos o transplante de figado

AUTOR(ES)
DATA DE PUBLICAÇÃO

2004

RESUMO

Background - In liver transplant, a large number of studies has demonstrated allogeneic microclrimerism. Clinical and immunological implications remain inconclusive; on the other hand, influence of HLA mismatch and donor alloreactivity also remain conf1icting. On the basis of these controversial data, the present study analyzed the presence of allogeneic microclrimerism in liver .transplant and prospectively investigated donor leukocyte kinetics related to rejection episodes. This study was extended into determining the influenceof immunogenetic factors in patients afier tiver transplant. Methods - Presence of allogeneic microclrimerism, influence of HLA alleles and donor specific anti-HLA antibodies were analyzed involving 50 donor/recipient pairs during a period of three years and two months. Analyses were carried out in peripheral blood of recipients. DNA was extracted from the samples and typing of HLA-DRBl and -DQBl alleles was obtained by Polymerase Chain Reaction using Sequence-Specific Primer (PCR/SSP). Microclrimerism was identified through nested PCR/SSP. The Complement- Dependent Cell Cytotoxicity (CDC) test was used to determine Panel Reactive Antibodies (PRA) of T and B cells. Results - Microclrimerism was detected in 72% of patients and the effect of microclrimerism on rejection episodes was found to be significant (p=0.002), while the eifect of HLA mismatch did not show to be significant, with one or two mismatches (p=0.98). Recipients with HLA-DRBl *01 (p=0.002), DRBl *04 (p=0.003), and DQBl *03 (p=0.002) alleles showed decreased frequencies when compared to control individuaIs. Recipients with the HLA-DQB1*02 allele (p=0.04) showed an increase of that allele in relation to healthy controls. Further, recipients carrying the HLA-DRBl *15011 allele showed a highly significant risk factor (p=0.007) in relation to development of tiver transplantation. Finally, eifects of donor specific anti-HLA antibodies on tiver transplant were not evident. Conclusion - The present study showed that the nested PCR/SSP method was sensitive in detection of allogeneic microchimerism,and that phenomenon was observed in the majority of examined patients. Allogeneic microclrimerismwas significantly associated to rejection episodes in post tiver transplant patients. Analysis of HLA mismatch demonstrated a decrease in rejection episodes in patients with a larger number ofHLA-DRBl and -DQBl mismatches. The HLA-DRBl *15 allele was associated to a highly significant risk factor in liver transplantation and survival time extension was greater in male patients. However, a more specific investigation of allogeneic microchimerism and anti-HLA antibodies is necessary, due to the fact that certain HLA genes seem to play a role in the nature and severity of diseases related to liver transplantation

ASSUNTO(S)

histocompatibilidade rejeição de enxertos biologia molecular

ACESSO AO ARTIGO

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