Glanzmann thrombasthenia and isoimmunization

Abstract

Glanzmann thrombasthenia is a rare autosomal recessive inherited bleeding disorder characterized by the inability of the platelets to aggregate. The abnormality results from a quantitative or qualitative defect in the platelet membrane glycoprotein (GP) IIb-IIIa. A potential consequence of platelet membrane GP deficiency is isoantibody (isoAb) production following platelet transfusion or during pregnancy, when the patient has contact with normal platelets. IsoAb have been reported in Glanzmann's thrombasthenia patients lacking GPIIb-IIIa (GTI), which recognize distinct epitopes on the GPIIb-IIIa complex. These antibodies (Ab) are of clinical significance as they can lead to platelet refractoriness by destruction of the transfused platelets and thus to therapeutical difficulties. The development of antigen specific assays (as the MAIPA technique) has been extremely useful, allowing the binding of the antibody to its epitope in a conformational state. One of the major disadvantages of this technique is the existence of false negative results due to a competition between the human Ab and monoclonal antibodies (MoAbs) for the same or closely related epitopes. Negative or discordant results for identification or characterization of Ab are a matter of concern during investigation for isoimmunization. In an attempt to demonstrate the importance of the choice of MoAbs for accurate biological diagnosis and to show the serological heterogeneity among isoAb, we screened serum from GTI patients by the MAIPA technique with a panel of MoAbs. These studies were particularly informative as we found striking differences in the binding of the human Ab to their target antigen depending on the MoAbs present in the reaction. Furthermore the choice of MoAbs can be crucial for detecting a specific Ab in case of low reactivity or low titre. Further investigations are needed to clarify whether this heterogeneity plays a role in clinical conditions.