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The Duffy antigen receptor for chemokines, ACKR 1 ,– ‘Jeanne DARC ’ of benign neutropenia
Author(s) -
Rappoport Naama,
Simon Amos J.,
Amariglio Ninette,
Rechavi Gideon
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15730
Subject(s) - immunology , neutropenia , biology , allele , chemokine , null allele , receptor , inflammation , gene , genetics , chemotherapy
Summary Benign neutropenia, observed in different ethnic groups, is the most common form of neutropenia worldwide. A specific single nucleotide polymorphism, rs2814778 , located at the promoter of the ACKR 1 (previously termed DARC ) gene, which disrupts a binding site for the GATA 1 erythroid transcription factor, resulting in a ACKR 1 ‐null phenotype, was found to serve as a predictor of low white blood cell and neutrophil counts in African‐Americans and Yemenite Jews. Individuals with benign neutropenia due to the ACKR 1 ‐null allele have been found to have an increased susceptibility to human immunodeficiency virus infection and, on the other hand, a protective effect against malaria. The associated protective effect may explain the spread of the ACKR 1 ‐null allele by natural selection. The reviewed relationships between ACKR 1 polymorphism and various pathological states may have important clinical implications to individuals with and without benign neutropenia. Potential mechanisms for ACKR 1 (previously termed DARC ) modulation during neutrophil recruitment to inflammation, and chemokine bioavailability in the circulation and in local tissue are reviewed and discussed.