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Lewis Blood Group System and Secretor
Swisstransfusion 2012
Dr. J.-P. Sigle
07.09.2012
How I got to meet Lewis
How I got to meet Secretor
How I got here
Today’s Topics
• Biochemistry and Pathways of Lewis and Secretor • Clinical Significance • Significance in Transfusion Medicine
You can separate them….
http://ibgrl.blood.co.uk/isbt%20pages/isbt%20home.htm
...but you shouldn’t! (Part 1)
3--N-Acetylgalaktosaminyl-transferase (A-Transferase)
3--N-Galaktosyltransferase (B-Transferase)
1-3
1-4 GlcNAc Gal
Fuc
1-2
GalNAc 1-3
1-4 GlcNAc Gal
Fuc
1-2
Gal
BG A BG B
1-3
1-4 GlcNAc Gal Gal R
Fuc
1-2
FUT-1:
-1-2-Fucosyltransferase
BG O
H-Substance
GlcNAc Gal Gal 1-3
1-4
R
Typ-2
H-Precursor-Substance
...but you shouldn’t! (Part 2)
H-Precursor / Non-Secretor
GlcNAc Gal Gal 1-3
R 1-3
Typ-1
FUT-2 (Se):
-1-2-Fucosyltransferase
FUT-3 (Le):
- 1-4-Fucosyltransferase
Lea
GlcNAc Gal
Fuc
1-4
R
1-2
GlcNAc Gal
Fuc
Fuc
1-4
FUT-3 (Le):
- 1-4-Fucosyltransferase
Leb
R
GlcNAc Gal
Fuc
1-2
H-Substance / Secretor
R 1-3
Typ-1
B-Substance A-Substance
Fuc
1-2
1-3 1-3 GlcNAc Gal Gal R
H-Substance / Secretor Typ-1
Finally united!
1-3 1-3 GlcNAc Gal
Fuc
1-2
GalNAc
A Substance
1-3 1-3 GlcNAc Gal
Fuc
1-2
Gal
B Substance
Fuc
1-4
1-3 1-3 GlcNAc Gal
Fuc
1-2
GalNAc
ALeb
1-3 1-3 GlcNAc Gal
Fuc
1-2
Gal
BLeb
Fuc
1-4
FUT-3 (Le):
- 1-4-Fucosyltransferase
Lewis Antigen Distribution
Combs (2009) Immunohematol 25:112
Tissue Expression • pancreas, stomach, intestinal mucosa • skeletal muscle, renal cortex, adrenal glands
Detection in • saliva, plasma • all body fluids except CSF Passive absorption from plasma • RBC, lymphocytes, platelets
Prevalence and Alleles
Combs (2009) Immunohematol 25:112
I do agree !
Combs (2009) Immunohematol 25:112
Lewis Antigens as Tumor Markers
= CA 19-9
Even Malaria ?
Cserti (2007) Blood 110:2250
I do not agree !
Henry (1995) Vox Sang 69:166
Changing colours
Henry (1995) Vox Sang 69:166
Lewis phenotype may be altered by • Pregnancy • Various cancers (pancreas, stomach, bile duct, breast,
colon, bladder) • Alcoholic pancreatitis, alcoholic cirrhosis, EBV infection
• Newborns (Sese; Lele): Cord Blood: Lea- Leb- 3 months: Lea+ Leb- 2 years: Lea+ Leb+ 6 years Lea- Leb+
Significance for Transfusion Medicine
Diagnose: Ph+ ALL
allogene HSZT 03.02.2006 (Fremdspender)
Blutgruppe D/R: 0+/A+
Significance for Plasma Transfusion ?
Shanwell et al (2009) Vox Sang 96:316
Conclusions
• Lewis and Secretor regulate Le antigen expression • Le and Secretor: prominent role in infection and cancer
• Le and ABH in secretion: pearls of transfusion medicine
Thank you for your attention !