Transfusion medicine

Red blood cell antigens

Duffy system


Editorial Board Member: Kyle Annen, D.O.
Deputy Editor-in-Chief: Patricia Tsang, M.D., M.B.A.
Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.

Topic Completed: 21 October 2021

Minor changes: 21 October 2021

Copyright: 2021, PathologyOutlines.com, Inc.

PubMed Search: Duffy blood group system[title]

Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.
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Cite this page: Adkins BD, Booth GS. Duffy system. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedduffysystem.html. Accessed November 27th, 2021.
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)

      Race / 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
      Adapted from Fung: Technical Manual, 19th Edition, 2017

    • Many individuals of African descent have the GATA1 mutation and an Fy(a-b+) genotype without phenotypic Fyb expression

  • Antibodies
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
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?

  1. Asian
  2. Black
  3. Native American
  4. 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
Board review style question #2
Duffy acts as a receptor for which species of Plasmodium (malaria)?

  1. P. falciparum / P. ovale
  2. P. malariae
  3. P. ovale
  4. P. vivax
Board review style answer #2
C. P. vivax

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