ACKR1/Duffy associated neutropenia (ADAN)

Intro

Common cause of the lower neutrophil counts commonly seen in people of African/Caribbean ethnicity

Not associated with increased risk of infection

Historically referred to as Benign Ethnic Neutropenia (BEN)

Normal Function

ACKR1 (Atypical Chemokine Receptor 1) gene codes for the Duffy blood group

Duffy is expressed by erythrocytes

Duffy regulates chemokine availability by acting as a reservoir for chemokines —> reducing/modulating chemokine concentration in the blood stream

ACKR1 mutation

Homozygous ACKR1 mutation = “Duffy Null Phenotype”

If ACKR1 is not expressed

  • Individuals have higher levels of circulating chemokines

  • —> increase neutrophil migration into tissues —> Reduces circulating numbers but not function

  • —> Chronic, asymptomatic “neutropenia”

The ACKR1 mutation also confers protection against P. vivax, malaria which may explain its geographical distribution.

Testing

Testing for ACKR1 mutation is not routinely available on the NHS (as of 2024)

Arguments in favour of testing include:

  • Explain cause of neutropenia and therefore reduce need for other tests

  • Personalised medicine - e.g. prior to prescribing drugs associated with neutropenia such as chemotherapy, anti-psychotics etc

Other Causes of Congenital Neutropenia

See list of inherited bone marrow failure syndrome on the Aplastic Anaemia page