The Lutheran Blood

Group System

Garcia, Alain Ian T.

Yor, Stephen Klent
BSMT 3-1
Objectives:
•Name the major antigens of Lutheran blood group system and list the
frequencies of the observed phenotypes.
•Describe carrier molecule structure and possible function for Lutheran
blood group system.
•Discuss biochemistry and genetics of Lutheran blood group system.
•Discuss the characteristics of antibodies associated with Lutheran blood
group system including:
◦ Serologic characteristics
◦ Clinical significance
◦ Special reagents and techniques useful in identification of the antibody
•Describe disease conditions associated with Lutheran blood group systems.
 The Lutheran Blood Group
System
•ISBT designation is ________or
LU 005
_______.
•1945- Lutheran _______
Ags Anti-Lu was
have been identified when _______
a

found in the serum of a patient with lupus erythematosus

•The new Ab was named Lutheran, a misinterpretation of the
Luteran
donor’s last name______.
Anti-Lub
•1956 -Cutbush and Chanarin came up Luawith the term _____ which
defined the antithetical partner to _______.
Lu(a-b-)
•1961- Crawford et al described the first _____phenotype. Unlike
most null phenotypes at the time, this demonstrated a dominant
inheritance.
•1963-Darnborough et al identified more traditional Lu(a-b-)
phenotype inherited as a recessive silent allele.
Basic Concepts
•In blood banking, it is rarely deal with the serology of the
Lutheran blood group system
o Antigens can either be very_____
High or very________
Low-incidence .
o Several Individuals have the antigen, so only a few are
capable of making alloantibody
_________.
o Antigens also have uncertain immunogenicity.
Genetics
•Lu gene is located on chromosome ____
19 at
position_________.
19q13.2-q13.3

•Together with genes involved in the expression of

several blood antigens (H, Se, Le, LW, Oka) and genes
for_____,
C3 apolipoprotein C-II, and___________.
myotonic dystrophy

•autosomal linkage in humans - linkage between Lu

and the Se gene (FUT2)
Lu(a-b-) Phenotypes
 Biochemistry
•Immunoblot methods and a monoclonal antibody (BRIC 108),
•initially appeared to have Lub-like activity
•Parsons et al105 identified two proteins (glycoproteins)
• Lutheran glycoproteins- contain both N- and O-linked
oligosaccharides and intrachain disulfide bonds.
•Subsequent immunoblotting with human antibodies to Lutheran
antigens has demonstrated that Lua, Lub, Lu3, Lu4, Lu6, Lu8,
Lu12, Aua (Lu18), and Aub (Lu19)107 are located on the Lutheran
glycoprotein.
 Lutheran Antigens
•Lu(_+)
a and Lu(_+)
b -developed by allelic________genes.
Codominant

•Found on fetal RBCs as early as ____ 10-12 weeks of gestation.

However,Poorly
_________
developed at birth and don’t reach adult levels.

•Present on, lymphocytes, monocytes or granulocytes by

means of sensitive RIA or imumunofluorescent techniques.
•Lutheran Glycoprotein- found in different tissues: brain,
lung, pancreas, placenta, skeletal muscle and hepatocytes
(especially fetal hepatic epithelial cells).
Lu6/Lu9 and Lu8/Lu14
•Lu6 and Lu8
◦ designations were assigned to two non-identical
antibodies directed against high-incidence antigens
related to the Lutheran system
•Anti-Lu9
◦ an antibody that reacted with 2 percent of random donors
and that gave very strong reactions with Lu:6 RBCs.
•Anti-Lu14
◦ antibody to a low-incidence antigen that was strongly
expressed on Lu:–8 RBCs.
 Aua (Lu18) and Aub (Lu19)
•Aua (Auberger)
◦ described by salmon et al in 1961 by
◦ antigen found in 80 percent of whites. In 1989 its antithetical antigen,
•Aub,
◦ was reported by Frandson et al.
◦ antigens were suppressed by In(Lu) and were destroyed by trypsin,
chymotrypsin, and pronase,
◦ closely associated with the Lutheran system except that, in one
family study, they were inherited independently.
◦ Serologists considered them another set of antigens suppressed by
Lutheran inhibitors.
 Aua (Lu18) and Aub (Lu19)
•Aua and Aub
◦ shown to be expressed on the Lutheran glycoprotein
◦ the Au(a) family members associated with the earlier genetic
exclusion were retested and found to test Au(a).
◦ Family linkage studies also demonstrated that the Auberger and
Lutheran antigens were controlled by the same gene.
 Other Lutheran Antigens
•Lu4, Lu5, Lu7, Lu12, Lu13, and Lu20
◦ antigens of very high incidence that are absent from Lu(a-b-) RBCs
◦ Not been shown to be inherited at the Lu locus.
◦ All have been shown to be located on the Lutheran glycoprotein, and all but Lu20
have been shown to be inherited. Their antibodies parallel the characteristics of
anti-Lu6 and anti-Lu8: they do not react with Lu(a-b-) RBCs or autologous cells,
which carry otherwise normal Lutheran antigens.
•Lu11, Lu16, and Lu17
◦ high-incidence antigens
◦ are phenotypically related to Lutheran.
◦ antigens are absent from Lu(a-b-) RBCs of the recessive
◦ In(Lu) types, notshown to be located on the Lutheran glycoprotein nor have they
been shown to be inherited;
◦ evidence that these antigens belong to the Lutheran system is thus very limited.
Other Lutheran Antigens
•An/Wj
◦ once associated with the Lutheran system
◦ it is not expressed or only weakly expressed on In(Lu) Lu(a-b-) RBCs
and was given the designation Lu15.
◦ became obsolete when An/Wj was found on LuLu RBCs.

•Lu10
◦ designation no longer used.
◦ reserved for Singleton, an antigen thought to be the allele of Lu5

•Lu5
◦ antibody reacted strongly with Lu:-5 RBCs.
◦ However, five other examples of Lu:5 cells were later tested and
found to be negative with the Singleton serum.
 Anti-Lua
•IgM naturally occuring saline agglutinins
•May be IgA,IgM or IgG
•reactive at room temperature than at 37oC.(few react at 37oC
IAT
by__________)
•Capable of binding compliment .
Most reagents are (Lu a-)
•Undetected in routine testing because_______________ .
•encountered as an incompatible crossmatch or during an
antibody workup for another specificity.
Mixed field reactivity
•Lutheran Ab by their characteristic loose, ___________ in a
test tube.
 Anti-Lua
•not profoundly altered with the common blood bank enzymes ficin and
papain,
•can be destroyed with trypsin, chymotrypsin, pronase, ____,
AET and ____.
DDT

•clinically insignificant in transfusion.

•poorly expressed on cord RBCs
•HDN cases associated with anti-Lua are ______.
MILD
◦ exhibit weakly positive or negative direct antiglobulin tests and mild to
moderate elevations in BLIRUBIN
______.
◦ Many require no treatment; others respond to simple phototherapy.
◦ the mother’s antibody titer rose to 4096.
 Anti-Lub
•Most are IgG (IgG_)
4
•IgM and IgA have been noted
•Reactive at 37oC at the antiglobulin phase
•Responds to pregnancy or transfusion.
•Alloanti-Lub interacts with all cells tested except the _________,
Autocontrol and
reactions are often weaker with _______
Lu(a+b+) RBCs and cord RBCs.
•Ficin or papain does not __________reactivity.
Alter
.
 Anti-Lub
•AET or DTT destroy Lub antigen through disruption of the disulfide bond
of the glycoprotein,
◦ require optimal conditions. Autologous RBCs will test Lu(a+) if typing
sera are available.
•Implicated with shortened survival of transfused cells and post-
transfusion jaundice,
◦ severe or acute ________
hemolysis has not been reported. Like anti-Lua, anti-
Lub is associated with only mild cases of HDN.
Anti-Lu3
•Rare Ab that reacts with all RBCs except those testing
Lu(a-b-).
•inseperable anti-Luab
•recognizes a common Ag, Lu3, that is present
whenever Lua or Lub is present.
•Usually antiglobulin-reactive
•Made only by LuLu individuals.
References
•Quinley et al, Immunohematology Principles and Practice, 3rd edition.
•Harmening, Blood Banking and transfusion practices, 7th edition.
•Paula Howard 4th Edition
•Henry’s 23rd edition
•https://www.britannica.com/science/Lutheran-blood-group-system
•https://www.britannica.com/science/blood-group