Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS) (TAAS)

Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS)

Anti-αIIbβ3 Immunization in Glanzmann Thrombasthenia: Prevalence and Associated Risk Factors: Thrombasthenia Anti-αIIbβ3 Antibodies Study (TAAS)

This project aim to correlate risk factors (genetic, therapeutic and socio-demographic factors) to anti-αIIbβ3 antibodies formation following blood products transfusion (platelets or packed red cells) or pregnancy in a national cohort of GT patients.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder caused by the absence or the dysfunction of the αIIbβ3 integrin, the most abundant receptor on platelets that mediates platelet aggregation through its binding of adhesive proteins. GT is readily identifiable by platelet function testing, and a lack of platelet aggregation in response to all physiological agonists is unique for this disease. The ITGA2B gene encodes for the αIIb subunit, whereas the ITGB3 gene encodes for β3. Mutations causing GT can affect either ITGA2B or ITGB3. The disease is characterized by spontaneous and trauma-related mucocutaneous bleeding, with variable expression ranging from easy bruising to fatal hemorrhages. Platelet transfusions are used to control or prevent life-threatening blood loss, but can become ineffective due to naturally occurring antibodies directed against αIIbβ3. Such antibodies are produced when patient's immune system comes into contact with normal αIIbβ3 expressing platelets. There is no currently consensus concerning the frequency, the long-term evolution, or the formation of characteristics of antibodies from GT patients in relation to the nature of the defective gene (ITGA2B or ITGB3), gene variations or other factors. Research are needed to confirm that nature of the gene defect may have a causative role in antibody development. Moreover, strength and persistence of antibodies may vary among patients with the same mutation, suggesting that other factors, such as immune modifiers genes, play a role in shaping antibody repertoire. Monoclonal antibody-specific immobilization of platelet antigens (MAIPA) is still considered as the reference method for evaluating the presence of anti-αIIbβ3 antibodies in GT patients. All the tests will be performed by the principal investigator site (Bordeaux).

Glanzmann thrombasthenia, anti-GPIIb-IIIa immunization, MAIPA, Platelet transfusions, Recombinant activated factor VII

Antibodies screening will be systematically realized every six months (+/- 2 weeks) and after each last blood transfusion at 7-10 days and one month (+/- 2 weeks), during a period of 18 months

All included GT patients will be enrolled from different national centres during a 6 months period. Antibodies screening will be systematically realized every six months (+/- 2 weeks) and after each last blood transfusion at 7-10 days and one month (+/- 2 weeks), during a period of 18 months.

Characterization of change of an anti-αIIbβ3 immunization will be assessed with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)

Presence of anti-αIIbβ3 antibodies will be assessed with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)

Repetition of the antibodies measurements with Indirect MoAb-specific immobilization of platelet antigens (MAIPA)

Determination of the mechanism of anti-αIIbβ3 antibodies blocking integrin function by determining the capacity of anti-αIIbβ3 antibodies to impair fibrinogen binding

In vitro studies will be performed by mixing serum of patients with washed donors' platelets and inhibition of the integrin will be studied by flow cytometry

Inclusion Criteria: All patients with a clear diagnosis of Glanzmann Thrombastenia (GT), whatever the subtype of disease. Affiliated person or beneficiary of a social security scheme. Free, informed and written consent signed by the participant, or parents or legal representant for the child population, and the investigator (at the latest on the day of inclusion and before any examination required by the research). Exclusion Criteria: Current treatment that may interfere with anti-αIIbβ3 antibodies detection, such as intravenous immunoglobulins within the previous month. Psychiatric, social or behavioral condition judged to be non-compatible with the respect of the protocol, including good observance of treatment and compliance to follow-up. Adult protected by the law.