RESUMO
BACKGROUND: This study aimed to establish the prevalence and characteristics of anti-HLA in antibody acquired aplastic anemia patients following cessation of antithymocyte globulin therapy and to characterize antibody in terms of epitope specificity. STUDY DESIGN AND METHODS: One hundred and fifty multitransfused, untransplanted patients from eight European centers were investigated by serologic methods. RESULTS: Sixty-two percent were antibody positive. Eighteen HLA-Class-I-specific antibodies (15 IgG, 3 IgM) were identified in 13 patients; 13 antibodies were specific for HLA-A epitopes and 5 for HLA-B. Epitope analysis identified significant correlation between serum reactivity and amino acid substitutions associated with HLA-Class-I epitopes. An excess of antibodies to HLA-A1-associated cross-reactive groups was identified. There was no significant difference in antibody frequency in patients taking cyclosporine compared to those who were not. CONCLUSION: Data suggested a contribution from B cell memory of alloantigens introduced during pregnancy. In some cases, antibody production continued many years after the last transfusion, and although the target varied between individual patients, the antibody to HLA was focused on a few specific Class I epitopes, the majority of which mapped to the HLA-A molecule.
Assuntos
Anemia Aplástica/imunologia , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Reação Transfusional , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Anemia Aplástica/sangue , Anemia Aplástica/terapia , Especificidade de Anticorpos , Soro Antilinfocitário , Estudos Transversais , Europa (Continente) , Feminino , Antígenos HLA/química , Antígenos HLA-D/imunologia , Histocompatibilidade , Humanos , Imunização , Epitopos Imunodominantes/química , Epitopos Imunodominantes/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Isoanticorpos/sangue , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/imunologia , Complicações Hematológicas na Gravidez/terapia , Prevalência , Distribuição Aleatória , Linfócitos TRESUMO
We prospectively followed 64 patients who had had no cytotoxic antibodies prior to first cadaveric renal allograft transplantation for post-transplant antibodies. During a mean follow-up period of 62 months (range 45-92) cytotoxic antibodies developed in 36 patients (56%). Sixteen grafts were lost due to chronic vascular rejection in the group of patients who developed antibodies compared to two in those who remained antibody negative, P < 0.01. Renal function was worse in the antibody-positive group, median serum creatinine 215 mumol/l (131-256) (interquartile range) versus 111 mumol/l (98-127) in the antibody-negative group, P = 0.002, and creatinine clearance 39 ml/min (25-55) versus 90 ml/min (55-104), P < 0.001. There were no significant differences in immunosuppressive protocol, HLA-mismatching, blood transfusion history, the number of acute rejection episodes, mean arterial blood pressure, or proteinuria between the groups. The presence of cytotoxic antibodies predated the classical manifestations of chronic vascular rejection. This suggests that humoral mechanisms may play a role in the development of chronic vascular rejection.
