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- Kjeldsen-Kragh, Jens, et al.
(författare)
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Mechanisms and prevention of alloimmunization in pregnancy.
- 2013
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Ingår i: Obstetrical and Gynecological Survey. - 0029-7828. ; 68:7, s. 526-532
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Tidskriftsartikel (refereegranskat)abstract
- Transfusion only occasionally gives rise to antibody production, because blood cells per se are not markedly immunogenic. However, the immunological changes that occur during pregnancy increase the risk of alloimmunization against red blood cells, platelets, and/or leukocytes. Fetal-maternal bleeding during pregnancy or in relation to delivery is the antigenic stimuli for immunization against red blood cells, whereas other mechanisms, such as trophoblast-derived microparticles, may also play a role in the production of antibodies against platelets. Antibody-mediated immune suppression has for 4 decades successfully been used for prevention of RhD immunization. Result from a mouse model of fetal and neonatal alloimmune thrombocytopenia (FNAIT) suggests that the same principle may be applied for the prevention of FNAIT. A European Union-funded consortium is presently in the process of developing a hyperimmune anti-human platelet antigen 1a (HPA-1a) immunoglobulin G. The idea is to prevent HPA-1a immunization by administering the drug to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. The anti-HPA-1a will be purified from plasma collected from women who previously have given birth to a child with FNAIT caused by anti-HPA-1a. If the results of the planned phase III trial are favorable, it is possible that a product for prevention of FNAIT will be available within this decade.
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| 3. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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Towards a prophylactic treatment of HPA-related foetal and neonatal alloimmune thrombocytopenia.
- 2012
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Ingår i: Current Opinion in Hematology. - 1531-7048. ; 19:6, s. 469-474
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The purpose of the review is to show the similarities between haemolytic disease of the foetus and newborn (HDFN) and foetal and neonatal alloimmune thrombocytopenia (FNAIT) and to describe the background and challenges related to the current endeavours of developing a prophylaxis against FNAIT. The rationale for this prophylaxis is similar to the prophylaxis which has been used with great success for the last 40 years against RhD-associated HDFN. The idea is to prevent human platelet antigen (HPA)-1a-associated FNAIT by administering anti-HPA-1a immunoglobulin G (IgG) to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. RECENT FINDINGS: Results from a Norwegian screening and intervention study on FNAIT have indicated that about 75% of women with antibodies against HPA-1a are immunized in relation to delivery. This observation leads to the possibility of preventing HPA-1a-associated FNAIT in the same way as today's prevention of HDFN. Results from a proof-of-concept study in a murine FNAIT model have shown that the production of alloantibodies against platelets can be suppressed by administrating antiplatelet antibodies after the antigenic challenge. Even more interesting, the prophylactic antiplatelet antibodies could also significantly reduce the clinical consequences of FNAIT in this FNAIT model. SUMMARY: These novel observations have paved the way for clinical studies. Production and testing of anti-HPA-1a IgG for clinical use will be carried out by a European Union-funded consortium. If the results from the clinical trial are favourable, there is a chance that a medicinal product for the prevention of FNAIT will be available within this decade.
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