Platelet and neutrophil alloantigen genotyping in clinical practice

Abstract

Immune responses to platelet and neutrophil alloantigens are involved in the pathogenesis of several clinical syndromes including: neonatal alloimmune thrombocytopenia (NATP), post-transfusion purpura (PTP), refractory responses to platelet transfusion, neonatal alloimmune neutropenia (NAN), transfusion-related acute lung injury (TRALI), and chronic benign autoimmune neutropenia of infancy. Initially, platelet alloantigens were only characterized serologically. Subsequently, they were localized to specific platelet surface glycoprotein structures and ultimately defined to the level of nucleic acid polymorphisms on platelet glycoprotein genes. These advances allowed the tools of molecular biology to be applied to typing for platelet alloantigens. The advantages of such typing methods include: 1) patient platelets are no longer required for the typing assays, and therefore, platelet types can be established on extremely thrombocytopenic samples (by using peripheral blood white blood cells [WBC]); 2) The genotyping methods eliminate the requirement for rare serologic reagents. A number of different genotyping methods have been developed. These include: restriction fragment length polymorphism (RFLP), sequence specific primers (SSP), and Dot-Blot hybridization. Clinical applications of this methodology include: determining the platelet genotype of fetuses at risk for NATP, in the diagnosis of PTP, and identifying causes of refractory responses to platelet transfusions. Analogous to platelet alloantigens, a limited number of neutrophil alloantigens can now be determined by molecular biologic methods. The new methods obviate the need to isolate fresh neutrophils for serologic typing and do not require rare serologic reagents. To date, molecular polymorphisms associated with alloantigens on the neutrophil Fc gamma RIIIb surface glycoprotein have been elucidated. These include the allo-antigens NA1, NA2, and SH.