Human Platelet Alloantigens: Recent Findings, New Perspectives

Human platelets are key participants in the primary hemostatic process and are armed with a large battery of cell surface adhesion molecules that mediate adhesion to extracellular matrix components and to each other. Serological studies initiated over 30 years ago provided the first evidence that the platelet surface, in addition to being adhesive, is also polymor­ phic and contains alloantigenic proteins that can be recognized as immunologic targets in a transplant setting — broadly defined. These platelet alloantigens are clinically important in that they can elicit the production of alloantibodies that lead to platelet clearance and thrombocytopenia in three pathophysio­ logical conditions: post-transfusion purpura (PTP), neonatal alloimmune thrombocytopenia (NATP), and less frequently, post-transfusion refractoriness (for a detailed review of the clinical features of these disorders, see Ref. 1). The three-dimensional structure of functionally important platelet membrane glycoproteins provides a vast number of potential target sites for the binding of anti-platelet alloanti­ bodies, and nine different serologically defined human platelet alloantigen systems have been described to date. During the past five years, we and others have used platelet RNA PCR technology (2) to examine the mRNA sequences of those membrane glycoproteins thought to be polymorphic and have discovered that simple amino acid dimorphisms are associated with the expression of most o f the currently described, clinically important human platelet alloantigenic determinants. This review will highlight recent progress in elucidating the molecular basis for platelet alloantigenicity and will also address the evolutionary relationships of the allelic forms of several clinically important platelet membrane glycoproteins. As will become obvious, despite our newfound, molecularlybased understanding of membrane glycoprotein polymorphism, much remains to be learned about the way in which platelet polymorphisms elicit an alloimmune response, which itself may be more complex than previously realized.