Objective
- 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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences biochemistry biomolecules carbohydrates
- medical and health sciences clinical medicine transplantation
- medical and health sciences clinical medicine oncology leukemia
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