From the Guidelines
Benign ethnic neutropenia (BEN) is the constitutional cause of low white blood cell counts (WBCs) in African Americans, characterized by a genetic polymorphism in the Duffy Antigen Receptor for Chemokines (DARC) gene. This condition affects approximately 25-50% of individuals of African descent and is characterized by persistently lower neutrophil counts compared to reference ranges established primarily in Caucasian populations. The genetic variation associated with BEN evolved as a protective mechanism against malaria infection, as discussed in the context of genetic adaptations in African populations 1. Key points to consider include:
- BEN is caused by a genetic polymorphism in the DARC gene, specifically the Duffy-null trait (FY*B-67T/C), which is highly prevalent in African populations.
- Individuals with BEN do not experience increased rates of infection, impaired immune function, or adverse health outcomes despite their lower neutrophil counts.
- Clinicians should recognize this normal variant to avoid unnecessary diagnostic testing, bone marrow biopsies, or withholding of necessary treatments like chemotherapy.
- When evaluating WBC counts in African American patients, healthcare providers should consider using ethnicity-specific reference ranges rather than standard ranges to prevent misdiagnosis of neutropenia. It is essential to acknowledge the importance of characterizing genetic variation among individuals of diverse ancestral backgrounds to gain a better understanding of differential susceptibility to disease, as highlighted in the study 1. By recognizing BEN as a normal variant in African American populations, clinicians can provide more accurate diagnoses and effective treatment plans, ultimately improving patient outcomes and reducing healthcare disparities.
From the Research
Constitutional Cause of Low WBC in African Americans
- The condition known as "benign ethnic neutropenia" is a common cause of low white blood cell (WBC) count in individuals of African ancestry 2, 3, 4.
- This condition is characterized by an absolute neutrophil count (ANC) <1500 cells/μL, but it does not increase the risk of infection 2, 4.
- The lower ANC levels in African Americans are driven by the Duffy null [Fy(a-b-)] phenotype, which is protective against malaria and seen in 80% to 100% of those of sub-Saharan African ancestry 2, 5.
- Studies have shown that African Americans have lower normal ranges for WBC counts compared to European Americans, with a significant difference in reference intervals for different ethnicities 3, 6.
- The use of race-specific WBC and neutrophil count reference intervals is essential for proper diagnosis and clinical research, especially in areas with a high percentage of people of African descent 6.
Genetic Basis of Benign Ethnic Neutropenia
- Genetic association studies have identified the rs2814778 variant in the Duffy Antigen Receptor for Chemokines (DARC) gene as a key factor in the development of benign ethnic neutropenia 5.
- The DARC null red cell phenotype is associated with a preferential differentiation of erythroid progenitors to myeloid cells, leading to activated DARC null neutrophils egressing from circulation to the spleen and causing relative neutropenia 5.
- Gene expression analysis in neutrophils of individuals with and without benign ethnic neutropenia has shown similar profiles, except for low DARC expression in individuals with the condition 5.
Clinical Implications of Benign Ethnic Neutropenia
- Benign ethnic neutropenia can lead to unnecessary discontinuation of medications, such as clozapine, due to concerns about leucopenia 3.
- The recognition of benign ethnic neutropenia as a clinically insignificant condition can help reduce disparities in healthcare and improve treatment outcomes for African American patients 2, 4.
- Further research is needed to fully understand the implications of benign ethnic neutropenia in clinical practice and to develop guidelines for the management of this condition 4.