The Atypical Chemokine Receptor 1 (ACKR1) gene encodes a transmembrane protein found on red blood cells and endothelial cells. This protein functions as a receptor for inflammatory chemokines; however, it is signaling mechanism differs from that of a conventional receptor. Associated with the Duffy blood group system, it also plays a role in inflammation regulation. The FY*BES allele, prevalent among individuals of African descent, results in the cessation of Duffy antigen production, leading to the Fy(a–b–) phenotype, which has been associated with immune system alterations. In autoimmune hemolytic anemia, the presence or absence of the Duffy antigen influences the severity of red blood cell destruction and the subsequent immune response.

The objective of this study is to ascertain the potential role of the ACKR1 gene in the regulation of the immune system and its association with the process of hemolysis, defined as the breakdown of red blood cells in patients diagnosed with autoimmune anemias.

A comprehensive review of studies from 2019 to 2025 was conducted using the databases PubMed, SciELO and LILACS. The following words were used to describe the project: The keywords “ACKR1”, “chemokines” and “autoimmune hemolytic anemia”, were entered into the search engine. A total of 17 articles were identified using the specified descriptors, however, only five of these were ultimately selected for further analysis.

Research demonstrated a correlation between a specific trait, designated as the Fy(a–b–) and phenotype, and the absence of a particular protein on red blood cells, known as Duffy. This absence has significant consequences for the immune system. The manner in which certain cells within the body adhere to one another may undergo alterations, potentially impeding the body's ability to regulate inflammation and compromising the functionality of the immune system. A substantial body of research has indicated that an insufficient intake of a specific protein, known as Duffy antigen, may result in elevated levels of chemical mediators that trigger inflammatory responses within the body. These elevated levels have the potential to render the immune system more susceptible to self-attack. When combined with genetic susceptibility, this condition can contribute to the breakdown of immune tolerance and the onset of red blood cell destruction caused by autoantibodies. Discussion: This phenomenon can result in an immune system that is more active, which can increase the likelihood of sensitivity to certain substances, particularly in individuals who are genetically predisposed to such reactions. Conclusion: The absence of Duffy antigen expression on red blood cells may play a significant role in the process of inflammation and the autoimmune causes of certain types of anemia. Genetic testing for the Duffy gene in patients with AIHA enhances medical professionals’ understanding of the condition and improves knowledge of potential autoimmune disease risks.