Cel - To establish a clinical database and depository of biological samples from patients with aplastic anaemia (AA) in the European Union.- To estimate the prevalence of deficiency of phosphatidyl-inositol glycan anchored proteins (PIG-AP) and PIG-A gene mutations and the effect of these on disease progression and treatment outcome. - To establish the prevalence and analyze the immunological specificity of, transfusion induced humoral allo-immunity to HLA in AA and to evaluate its relationship to transfusion resistance (TR). - To examine the effectiveness of therapeutic protocols designed to avoid TR.Both haematological (Section A) and immunological (Section B) aspects of AA are to be studied. Both will refer to a clinical database consisting of details of patients with AA in the EU. In Section A, PIG-AP deficient populations of blood cells will be identified by flow cytometry using a battery of monoclonal antibodies directed towards PIG-AP's. 105 patients will be sampled at the following time points; diagnosis, 4 months after immunosuppressive therapy, or bone marrow transplantation and thereafter at six monthly intervals. PIG-AP analysis will also be performed in the event of relapse, occurrence of clinical or serological paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) or acute leukaemia. 60 healthy volunteers will be analyzed in parallel. PIG-AP expression will be analyzed on all nucleated blood cells including granulocytes. In patients with PIG-AP deficient cell populations DNA analysis of PIG-A genes will be performed initially by SSCP analysis of 6 PCR amplified exons and subsequently by sequencing defective DNA after cloning into pGEM19. The major task is to analyze PIG-A gene mutations in relation to the outcome of the disease (response to immunosuppression, relapse, clinical PNH, evolution of malignant clonal disorders). In section B, 500 multiply transfused patients with AA who have not been transplanted will be studied to establish the incidence of transfusion resistance (TR). Sera will be screened for the presence of HLA Class I and Class II allo-antibodies, and in positive sera the specificity of antibody will be defined. The molecular epitopes responsible for allo-antibody reactions will be further investigated using computer analysis. Clinical transfusion protocols will be surveyed and a prospective study of transfusion practice undertaken on 100 newly diagnosed AA patients. Transfusion protocols, onset of transfusion resistance, haemorrhage and survival will be monitored. Sequential blood samples will be taken to detect the development of allo-antibodies which will be correlated with clinical outcome. Dziedzina nauki natural sciencescomputer and information sciencesdatabasesmedical and health sciencesbasic medicinephysiologypathophysiologynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicinetransplantationmedical and health sciencesclinical medicineoncologyleukemia Program(-y) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Temat(-y) 4.6.1 - Basic and clinical research in rare diseases Zaproszenie do składania wniosków Data not available System finansowania CSC - Cost-sharing contracts Koordynator N/A Wkład UE Brak danych Adres Zobacz na mapie Koszt całkowity Brak danych Uczestnicy (3) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko Azienda Ospedaliera Ospedale San Martino di Genova e Cliniche UniversitarieConvenzionate Włochy Wkład UE Brak danych Adres Piazzale Rosanna Benzi 10 16132 Genova Zobacz na mapie Koszt całkowity Brak danych University of Bristol Zjednoczone Królestwo Wkład UE Brak danych Adres Westbury-on-Trym BS10 5NB Bristol Zobacz na mapie Koszt całkowity Brak danych University of London Zjednoczone Królestwo Wkład UE Brak danych Adres Cranmer Terrace SW17 0RE London Zobacz na mapie Koszt całkowity Brak danych
