Transfusion medicine
Red blood cell antigens
Lewis system
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PubMed Search: Lewis antigens [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. Lewis system. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/transfusionmedicinelewis.html. Accessed April 1st, 2025.
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)
- Most antibodies are IgM, which does not cross into fetal circulation; Lewis antigens are not expressed extensively on fetal red cells
- Single report of HDFN with Lea (Reid: The Blood Group Antigen FactsBook, 3rd Edition, 2012)
- 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
Adapted from Fung: Technical Manual, 19th Edition, 2017Race / 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
- Antibodies
- Majority are IgM but some are IgG (Lea > Leb) and not clinically significant
- Lewis substance circulates freely in the plasma and can readily bind antibodies without associating with RBCs
- Lewis antigens are not strongly expressed on cord blood cells, effectively preventing HDFN, even in the presence of an IgG component (Reid: The Blood Group Antigen FactsBook, 3rd Edition, 2012)
- Occur with exposure to products containing incompatible blood; naturally occur during pregnancy (Fung: Technical Manual, 19th Edition, 2017)
- Rare reports of hemolytic transfusion reactions; a single report of HDFN with Lea (Reid: The Blood Group Antigen FactsBook, 3rd Edition, 2012)
- Majority are IgM but some are IgG (Lea > Leb) and not clinically significant
- 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
- Levels can decrease during pregnancy or with increased plasma volume; patient's cells may phenotype as Lea-Leb-
- Lewis antigen levels decrease with red cell storage and therefore phenotyping is most reliable on fresh units
- Lewis antibodies can sometimes cause in vitro hemolysis (Lea > Leb)
- References: Fung: Technical Manual, 19th Edition, 2017, Kreuter: Transfusion Medicine Self-Assessment and Review, 2017
Case reports
- 19 year old man, a blood donor, was found to have clinically significant anti-Leb causing transfusion reaction (Asian J Transfus Sci 2020;14:198)
- 21 - 65 year old patients with Lewis system antibodies (Asian J Transfus Sci 2020;14:54)
- 30 year old African American woman with acute hemolytic transfusion reaction due to anti-Le(b) (Transfusion 2015;55:2486)
- 31 year old woman with Le(a-b+) phenotype and novel para-Bombay phenotype (Transfus Med Hemother 2021;48:254)
Additional references
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?
- Counsel the patient that these antibodies do not cause hemolytic disease of the fetus and newborn (HDFN)
- Percutaneous umbilical cord blood sampling
- Serial titers
- 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.
Comment Here
Reference: Lewis
Comment Here
Reference: Lewis
Board review style question #2
Lewis antigen b (Leb) acts as a receptor for which microorganism?
- Brachyspira aalborgi
- Giardia lamblia
- H. pylori
- P. ovale
Board review style answer #2
