Transfusion medicine
Red blood cell antigens
Duffy system
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PubMed Search: Duffy blood group system[title]
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Clinical features | Transmission | Laboratory | Case reports | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Adkins BD, Booth GS. Duffy system. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedduffysystem.html. Accessed November 27th, 2024.
Definition / general
- Duffy blood group antigens are found on a glycoprotein on the surface of red blood cells and other cells in the body
- Antibodies clinically significant
Essential features
- Duffy antigens are common in whites but uncommon in the black population
- Antibodies can cause hemolysis and hemolytic disease of fetus and newborn (HDFN)
- Duffy acts as a receptor for malaria species, specifically Plasmodium vivax
- Mutations in the GATA1 promoter gene block red cell localization of Fyb
Terminology
- Duffy a, Fya or Fy1
- Duffy b, Fyb or Fy2
Pathophysiology
- GATA1 acts as a promoter for transcription of the Fyb antigen
- Point mutations in GATA1 disrupt binding of an erythroid transcription factor, which leads to a block in expression of Fyb in red cells (Fyb silent allele)
- As Fyb is expressed on other tissues throughout the body, these individuals should not produce Fyb antibodies
- Reference: Fung: Technical Manual, 19th Edition, 2017
Clinical features
- Duffy acts a receptor for P. vivax and P. knowlesi
- Antigens (type: peptide)
- 2 common antigens: Fya and Fyb, which are prevalent in the white population but less commonly expressed on red blood cells in individuals of African descent as a result of evolutionary pressures caused by malaria (Fung: Technical Manual, 19th Edition, 2017)
- Duffy glycoprotein is encoded by the ACKR1 (atypical chemokine receptor 1) gene on chromosome 1q21-q22 and acts as a transmembrane chemokine receptor (Fung: Technical Manual, 19th Edition, 2017)
- Duffy protein acts as a receptor for P. vivax and P. knowlesi; emerging data demonstrates that Duffy negative individuals can still be infected by P. vivax (Hematology 2006;11:389, Malar J 2020;19:229)
- Individuals of African descent commonly have mutations in the GATA1 gene, which normally acts as a promoter for erythroid transcription of the Fyb gene
- Inactivating GATA1 mutations turns off Fyb antigen expression on red cells only while other tissues continue to express it
- These individuals do not form Fyb antibodies and are protected from alloimmunization (Fung: Technical Manual, 19th Edition, 2017)
- True Duffy null individuals can form antibodies to Fy3, Fy4, Fy5 and Fy6, with Fy3 and Fy5 being clinically significant (Fung: Technical Manual, 19th Edition, 2017)
- The genes for Duffy may play a role in maintaining adequate neutrophil counts and there is an association between Duffy null individuals and benign ethnic neutropenia (BEN) (Blood Rev 2019;37:100586)
Adapted from Fung: Technical Manual, 19th Edition, 2017Race / Ethnicity Fy(a+b-) Fy(a+b+) Fy(a-b+) Fy(a-b-) White 20 48 32 Rare Black (U.S.) 10 3 20 67
- Many individuals of African descent have the GATA1 mutation and an Fy(a-b+) genotype without phenotypic Fyb expression
- Antibodies
- Majority IgG1 (Fung: Technical Manual, 19th Edition, 2017)
- Occur with exposure to products containing incompatible blood or pregnancy; rarely naturally occurring (Fung: Technical Manual, 19th Edition, 2017)
- Anti-Fya antibodies are most common (Fung: Technical Manual, 19th Edition, 2017)
- Fy3, Fy4, Fy5 and Fy6 antibodies can be formed in Duffy null individuals; Fy3 and Fy5 are clinically significant
Transmission
- Exposure to Duffy antigens secondary to pregnancy or transfusion
Laboratory
- Serologic phenotyping must be taken to the antihuman globulin phase and cannot be performed in the presence of a positive direct antiglobulin test (DAT); there has been interest in developing antibodies as a workaround (Br J Haematol 2004;126:277, Immunohematology 2006;22:161)
Case reports
- 24 year old woman with HDFN due to multiple alloantibodies, including Fya (Asian J Transfus Sci 2020;14:83)
- 69 year old woman with Fya antibodies who expired due to TRALI (Transfusion 2021;61:1336)
- 77 year old man with delayed hemolytic transfusion reaction with Fya antibodies successfully treated with automated red blood cell exchange (Arch Pathol Lab Med 2013;137:861)
- 10 cases of P. vivax in Duffy negative individuals (Am J Trop Med Hyg 2018;99:1128)
- Blood donor found to have novel Duffy antigen (Transfusion 2019;59:2158)
Additional references
Board review style question #1
A patient is found to have a Fya antibody. Blood from what group of donors would most likely be compatible?
- Asian
- Black
- Native American
- White
Board review style answer #1
B. Black. Negativity for Duffy antigens is most common in African individuals due to environmental pressures exerted by malaria. Fya antigen positivity is common in White, Asian and Native American populations.
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Reference: Duffy system
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Reference: Duffy system
Board review style question #2
Duffy acts as a receptor for which species of Plasmodium (malaria)?
- P. falciparum / P. ovale
- P. malariae
- P. ovale
- P. vivax
Board review style answer #2
