The Lutheran (005) Blood Group

System
The ISBT designation is LU or 005.
Lutheran Ags have been recognized since 1945 when the first
example of an anti-Lu
a
was discovered in the serum of a
patient with lupus ertythematosus diffusus, following the
transfusion unit of blood carrying the corresponding low-
incidence antigen.
The new Ab was named Lutheran, a misinterpretation of the
donors name Luteran.
In 1956 Cutbush and Chanarin described anti-Lu
b
which
defined the antithetical partner to Lu
a
.
Appeared complete until 1961 when Crawford et al described
the first Lu(a-b-) phenotype. Unlike most null phenotypes at
the time, this demonstrated a dominant inheritance.
In 1963 Darnborough et al found more traditional Lu(a-b-)
phenotype inherited as a recessive silent allele.
Basic Concepts
Blood bankers seldom deal with the serology of the
Lutheran blood group system because the antigens are
either very high or very low-incidence. Either so many
people have the antigen, so only a few are capable of
making alloantibody, or the antigens are so rare that only
a few people are ever exposed. Consequently, the
antibodies are seen infrequently. The antigens also have
questionable immunogenicity.
Lu
a
and Lu
b
Antigens
Produced by allelic codominant genes. Most individuals
are Lu(b+); only a few are Lu(a+).
Can be detected on fetal RBCs as early as 10-12 weeks
of gestation but poorly develop at birth and dont reach
adult levels until age of 15.
Not detected on platelets, lymphocytes, monocytes or
granulocytes by means of sensitive RIA or
imumunofluorescent techniques.
Lutheran GP, however is widely distributed in tissues:
brain, lung, pancreas, placenta, skeletal muscle and
hepatocytes (especially fetal hepatic epithelial cells).
Anti-Lu
a
Most are IgM naturally occuring saline agglutinins that
react better at room temperature than at 37
o
C. A few
react at 37
o
C by indirect antiglobulin test. Some are
capable of binding complement but in vitro hemolysis
has not been reported.
Lutheran Abs are unusual in that they may be IgA as well
as IgM and IgG.
Anti-Lu
a
often goes undetected in routine testing
because most reagent cells are Lu(a-). Anti-Lu
a
is more
likely encountered as an incompatible crossmatch or
during an antibody workup for another specificity.
Experienced technologists recognize Lutheran
antibodies by their characteristic loose, mixed-field
reactivity in a test tube.

Anti-Lu
a

Anti-Lu
a
is not profoundly altered with the common blood
bank enzymes ficin and papain, but it can be destroyed
with trypsin, chymotrypsin, pronase, AET, and DTT. Most
Lu
a
antibodies are clinically insignificant in transfusion.
Because Lutheran antigens are poorly expressed on
cord RBCs, cases of HDN associated with anti-Lua are
mild. Infants may exhibit weakly positive or negative
direct antiglobulin tests and mild to moderate elevations
in bilirubin. Many require no treatment; others respond to
simple phototherapy. In one report of mild HDN, the
mothers antibody titer rose to 4096.

Anti-Lu
b

First example was room-temperature agglutinin and IgM and
IgM Abs have noted.Most Anti-Lu
b
is IgG and reactive at 37
o
C
at the antiglobulin phase and is made in response to
pregnancy or transfusion.
Alloanti-Lu
b
reacts 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 significantly alter reactivity.
AET or DTT should destroy Lu
b
antigen through disruption of
the disulfide bond of the glycoprotein, but this may require
optimal conditions. Autologous RBCs will test Lu(a+) if typing
sera are available.
Has been implicated with shortened survival of transfused
cells and post-transfusion jaundice, but severe or acute
hemolysis has not been reported. Like anti-Lu
a
, anti-Lu
b
is
associated with only mild cases of HDN.
Biochemistry
Using immunoblot methods and a monoclonal antibody
(BRIC 108), which initially appeared to have Lu
b
-like
activity, Parsons et al105 identified two proteins with
molecular weights of 85 and 78 kD. These two
glycoproteins, now known as the Lutheran glycoproteins,
contain both N- and O-linked oligosaccharides and
intrachain disulfide bonds. Subsequent immunoblotting
with human antibodies to Lutheran antigens has
demonstrated that Lu
a
, Lu
b
, Lu3, Lu4, Lu6, Lu8, Lu12,
Au
a
(Lu18), and Au
b
(Lu19)107 are located on the
Lutheran glycoprotein.
Genetics
The Lu gene is located on chromosome 19 at position
19q13.2-q13.3, along with genes that govern expression
of several blood antigens (H, Se, Le, LW, Ok
a
) and
genes for C3, apolipoprotein C-II and myotonic
dystrophy. A linkage between Lu and the Se gene
(FUT2) was first example of autosomal linkage described
in humans.

Lu(a-b-)
Anti-Lu3
Rare Ab that reacts with all RBCs except those testing
Lu(a-b-). Looks like inseperable anti-Lu
ab
and recognizes
a common Ag, Lu3, that is present whenever Lu
a
or Lu
b

is present.
Usually antiglobulin-reactive
Made only by LuLu individuals.
Lu6/Lu9 and Lu8/Lu14
In 1972 Lu6 and Lu8 designations were given to two non-
identical antibodies directed against high-incidence antigens
related to the Lutheran system. The antibodies reacted with
all RBCs except autologous and Lu(a-b-) cells, but they were
made by Lu(a-b+) individuals.
In 1973 Molthan et al114 described anti-Lu9, an antibody that
reacted with 2 percent of random donors and that gave very
strong reactions with Lu:6 RBCs. In 1977 Judd et al described
anti-Lu14, another antibody to a low-incidence antigen that
was strongly expressed on Lu:8 RBCs.
Au
a
(Lu18) and Au
b
(Lu19)
Au
a
(Auberger) was described in 1961 by Salmon et al as an
antigen found in 80 percent of whites. In 1989 its antithetical
antigen, Au
b
, was reported by Frandson et al. Because the
antigens were suppressed by In(Lu) and were destroyed by
trypsin, chymotrypsin, and pronase, they were 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.
Au
a
and Au
b
were subsequently shown to be expressed on the
Lutheran glycoprotein, and 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 are antigens of very high
incidence that are absent from Lu(a-b-) RBCs, but they have 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.
The high-incidence antigens Lu11, Lu16, and Lu17 are
phenotypically related to Lutheran. These antigens are absent from
Lu(a-b-) RBCs of the recessive and In(Lu) types, but they have not
been shown 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
The An/Wj antigen was once associated with the
Lutheran system because it is not expressed or only
weakly expressed on In(Lu) Lu(a-b-) RBCs and was
given the designation Lu15; this became obsolete when
An/Wj was found on LuLu RBCs.
Lu10 is another designation no longer used. It was
reserved for Singleton, an antigen thought to be the
allele of
Lu5; the 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.