The Duffy antigen receptor for chemokines, ACKR1,– ‘Jeanne DARC’ of benign neutropenia

Naama Rappoport, Amos J. Simon*, Ninette Amariglio, Gideon Rechavi

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

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 ACKR1 (previously termed DARC) gene, which disrupts a binding site for the GATA1 erythroid transcription factor, resulting in a ACKR1-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 ACKR1-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 ACKR1-null allele by natural selection. The reviewed relationships between ACKR1 polymorphism and various pathological states may have important clinical implications to individuals with and without benign neutropenia. Potential mechanisms for ACKR1 (previously termed DARC) modulation during neutrophil recruitment to inflammation, and chemokine bioavailability in the circulation and in local tissue are reviewed and discussed.

Original languageEnglish
Pages (from-to)497-507
Number of pages11
JournalBritish Journal of Haematology
Volume184
Issue number4
DOIs
StatePublished - Feb 2019

Funding

FundersFunder number
Varda and Boaz Dotan Research Center
Tel Aviv University
Varda and Boaz Dotan Research Center for Hemato-Oncology Research, Tel Aviv University
Sackler Faculty of Medicine, Tel-Aviv University

    Keywords

    • ACKR1 polymorphism
    • Duffy null
    • FY allele
    • benign neutropenia
    • rs2814778

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