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 !