Transfusion medicine

Red blood cell antigens

Lewis


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.

Last author update: 18 April 2022
Last staff update: 18 April 2022

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PubMed Search: Lewis antigens [title]

Brian D. Adkins, M.D.
Garrett S. Booth, M.D., M.S.
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Cite this page: Adkins BD, Booth GS. Lewis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedicinelewis.html. Accessed February 3rd, 2023.
Definition / general
  • Lewis antigens are carbohydrates that are present in the plasma and adsorbed to the red cell surface
  • Antibodies are generally not clinically significant
Essential features
  • Lewis antigens are created by enzymatic modification of type 1 chains
  • Lewis antibodies are generally clinically insignificant
  • Levels drop with increase in plasma volume, specifically common in pregnancy
  • Lewis acts as a receptor for H. pylori
Terminology
  • Lea (LE1)
  • Leb (LE2)
Pathophysiology
  • Lewis antigens are carbohydrates synthesized from type 1 chains with the fucosyltransferase FUT3
  • Unmodified type 1 chains are converted to Lea, while H chains are converted to Leb
    • FUT2 (secretor) is more efficacious than FUT3 and therefore most type 1 chains are converted to H and Leb rather than Lea
    • Nonsecretors cannot produce Leb and only make Lea
    • Absence of FUT2 and FUT3 leads to the Le(a-b-) phenotype
    • Rarely patients have weak secretor activity and produce a Le(a+b+)
      • This phenotype is more common in Asian populations
  • Individuals with Leb typically have some Lea present, which may not be detected with serologic phenotyping
    • Lewis antigens are present in the plasma and secretions (e.g., saliva and milk) and passively adhere to the RBC surface
    • In order for individuals to elaborate Lewis A, unmodified type I chains must be modified by FUT3
    • To produce Lewis B, H antigens produced by individuals with the secretor gene (FUT2) are subsequently modified to form Lewis B antigens
    • FUT2 acts on type I chains more avidly and therefore most of the Lewis antigens produced in secretors with FUT3 are Lewis B, though a small proportion of Lewis A is likely present based on the low rate of anti-Lewis A in this population
  • Reference: Fung: Technical Manual, 19th Edition, 2017
Clinical features
  • Lewis antigens modify chains with FUT3 to form Lea and H to form Leb
  • Levels can decrease during pregnancy and patient’s cells may phenotype as Lea-Leb-
    • At this time, patients may develop Lewis antibodies, which are clinically insignificant
  • Not associated with hemolytic disease of the fetus and newborn (HDFN)
  • Leb acts as a receptor for H. pylori
  • Antigens (type: carbohydrate) (Fung: Technical Manual, 19th Edition, 2017)
    • 2 common antigens: Lea and Leb
    • Leb antigens can be modified by A and B enzymes leading to ALeb and BLeb

    Race / ethnicity Le(a+b+) Le(a+b-) Le(a-b+) Le(a-b-)
    White Rare 22 72 6
    Black (U.S.) Rare 23 55 22
    Adapted from Fung: Technical Manual, 19th Edition, 2017

  • Antibodies
  • Disease associations (Wiley Interdiscip Rev Syst Biol Med 2016;8:517):
    • Norovirus found to bind to Lewis antigens as well as A and H antigens
    • Lewis nonsecretors Le(a+,b-) may have more severe cholera infections and Lewis null individuals have more prolonged diarrheal illness
    • H. pylori lipopolysaccharide demonstrates mimicry of Lewis antigens leading to antibody formations; H. pylori infection is associated with extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) (Gut 2000;47:10)
Transmission
  • Exposure to Lewis antigens secondary to pregnancy or transfusion
Laboratory
Case reports
Board review style question #1
A pregnant woman is found to have a Leb antibody. The OB / GYN resident consults the blood bank for advice. What do you recommend?

  1. Counsel the patient that these antibodies do not cause hemolytic disease of the fetus and newborn (HDFN)
  2. Percutaneous umbilical cord blood sampling
  3. Serial titers
  4. Transcranial Doppler ultrasound
Board review style answer #1
A. Counsel the patient that these antibodies do not cause HDFN. Lewis antibodies tend to be IgM, which do not cross the placenta; likewise, fetal red cells do not express Lewis antigens. Pregnant patients may transiently develop Lewis antibodies later in their pregnancy.

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Reference: Lewis
Board review style question #2
Lewis antigen b (Leb) acts as a receptor for which microorganism?

  1. Brachyspira aalborgi
  2. Giardia lamblia
  3. H. pylori
  4. P. ovale
Board review style answer #2
C. H. pylori

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