AM24-TU-09-O: Duffy (ACKR1): Antibodies, Chemokines and Potential Therapeutic Targets-Not Just for Transfusion Anymore (Enduring)

Outside of Rh, the Duffy (Fy) blood group is one of the most important non-ABO blood groups worldwide. The Fy blood group protein is the receptor for Plasmodium vivax, and the RBC of those lacking the principal Fya and Fyb antigens on the RBC membrane are resistant to invasion, which is a likely explanation for the predominance of the Fy(a-b-) phenotype among people of African descent. Over the past thirty years the impact of Fy protein expression has become even more apparent. The Fy protein was identified as a member of the seven transmembrane domain chemokine receptor family that binds both C-X-C and C-C chemokines, resulting in its being referred to as the Duffy antigen receptor for chemokines (DARC). More recently, DARC has become known as the Atypical chemokine receptor 1 (ACKR1), and is now understood to be a key chemokine regulator involved in inflammatory responses, tumor angiogenesis and metastasis. In addition, ACKR1 is implicated in differences in neutrophil reference ranges, referred to as Duffy-null Associated Neutrophil Count (DANC), with studies underway to define relevant neutrophil reference ranges related to this RBC phenotype. Thus, the Fy antigens, once thought to be restricted to importance only in blood transfusion, likely have a much broader impact on disease.