Grant: Operating Grant - Priority Announcement: Blood Utilization and Conservation
Unity Health Toronto
$0.00
Pathogenesis and treatment of immune thrombocytopenia: Are there fundamental differences between anti-GPIba- and anti-GPIIbIIIa-mediated thrombocytopenia?
EF 2013-14
Résumé
Platelets are small blood cells responsible for forming clots at the site of bleeding. They aggregate to form a cellular plug, strengthen the coagulation system when blood vessels are injured, and are critical in preventing blood loss. Autoimmune thrombocytopenia (ITP) is a disease that occurs when the immune system mistakenly produces antibodies that destroy a patient's own platelets. Thus, the patient cannot stop bleeding, which can lead to severe problems or death. The antibodies in this disease attack two proteins (antigens), called GPIIbIIIa and GPIb, on the surface of platelets. These proteins are responsible for binding platelets together and sticking to the vessel wall to stop bleeding. Approximately 70-80% of ITP patients have antibodies targeting GPIIbIIIa, 20-40% of patients have antibodies targeting GPIb, and some patients have antibodies targeting both. Currently, it is not clear whether the antibodies to GPIIbIIIa and GPIb cause ITP by the same mechanism, nor whether ITP caused by each of these proteins can be successfully treated by the same therapies. We also do not know whether some patients have more severe bleeding than others because of the specific type of antibodies in their blood (i.e. whether severity is related to the protein or the subsection of the protein that the antibody attacks). We propose to address these questions and investigate whether antibodies against GPIb and GPIIbIIIa may act differently by: i) changing platelet signaling activity, ii) changing the physical structure of GPIIbIIIa and GPIb proteins, or iii) affecting platelet generation. We think that different antibodies may affect platelet function in a different manner, which determines where platelets are destroyed and how patients respond to current clinical therapies (e.g. removing the spleen or IVIG treatment). This study has already and will continue to provide significant insights into development of new diagnostic and therapeutic methods to control this disease.
Programme
Operating Grant - Priority Announcement: Blood Utilization and Conservation
Bénéficiaire
Emplacement
Ontario, Canada
Type de bénéficiaire
Other
Type
Grant
Source
CIHR Funding Decisions Database
Tel que publié
Id
309658
Name
Ni Heyu
Region
Ontario
Country
Canada
Orgtype
Institution Paid; Research Institution
Partnername
Canadian Blood Services (Ottawa)
Instname2
Circulatory and Respiratory Health
Theme2
Biomedical
Prcname2
Hematology, Digestive Disease & Kidney
Projecttitle
Pathogenesis and treatment of immune thrombocytopenia: Are there fundamental differences between anti-GPIba- and anti-GPIIbIIIa-mediated thrombocytopenia?
Programtype2
Operating Grants
Orgnameinp2
Unity Health Toronto
Cihramount2
$0
Cihrequipment2
$0
Programname2
Operating Grant - Priority Announcement: Blood Utilization and Conservation
Keyworddelim
Immune Thrombocytopenia (Itp): Autoimmune Bleeding Disorder; Intravenous Immunoglobulin G (Ivig); Monoclonal Antibody Epitope Mapping; Platelet Antigens: Gpiibiiia Versus Gpib; Platelet Clearance And Phagocytosis; Platelet Desialylation; Platelet Function; Platelet Generation
Abstract
Platelets are small blood cells responsible for forming clots at the site of bleeding. They aggregate to form a cellular plug, strengthen the coagulation system when blood vessels are injured, and are critical in preventing blood loss. Autoimmune thrombocytopenia (ITP) is a disease that occurs when the immune system mistakenly produces antibodies that destroy a patient's own platelets. Thus, the patient cannot stop bleeding, which can lead to severe problems or death. The antibodies in this disease attack two proteins (antigens), called GPIIbIIIa and GPIb, on the surface of platelets. These proteins are responsible for binding platelets together and sticking to the vessel wall to stop bleeding. Approximately 70-80% of ITP patients have antibodies targeting GPIIbIIIa, 20-40% of patients have antibodies targeting GPIb, and some patients have antibodies targeting both. Currently, it is not clear whether the antibodies to GPIIbIIIa and GPIb cause ITP by the same mechanism, nor whether ITP caused by each of these proteins can be successfully treated by the same therapies. We also do not know whether some patients have more severe bleeding than others because of the specific type of antibodies in their blood (i.e. whether severity is related to the protein or the subsection of the protein that the antibody attacks). We propose to address these questions and investigate whether antibodies against GPIb and GPIIbIIIa may act differently by: i) changing platelet signaling activity, ii) changing the physical structure of GPIIbIIIa and GPIb proteins, or iii) affecting platelet generation. We think that different antibodies may affect platelet function in a different manner, which determines where platelets are destroyed and how patients respond to current clinical therapies (e.g. removing the spleen or IVIG treatment). This study has already and will continue to provide significant insights into development of new diagnostic and therapeutic methods to control this disease.
Competitiondate
201403
Approvedterm2
3 yrs 0 mth
Pinamesdelim
Ni, Heyu
Approvedterm
3 ans 0 mois
