Unit 9 Other Blood Group Systems
Part 2
Terry Kotrla, MS, MT(ASCP)BB
Systems that Produce Cold-Reacting
Antibodies
Covered So Far
 I
 i
 Lewis
 P
MNSs Blood System (ISBT 002)
 4 important antigens (more exist):





M
N
S
s
U (ALWAYS present when S & s are inherited)
 Antibodies





M – antibodies USUALLY reactive at RT
N - antibodies USUALLY reactive at RT
S – antibodies are clinically significant
s – antibodies are clinically significant
U - antibodies are clinically significant
MNSs Antibodies – General Information
 All show dosage
 M & N give a stronger reaction when homozygous,
(M+N-) or (M-N+)
 Weaker reactions occur when in the heterozygous state
(M+N+)
 Antigens are destroyed by enzymes (i.e. ficin, papain)
Dosage
Cell
IS
37
IgG
1
M+N= (MM)
3+
1+
0
2
M+N+ (MN)
2+
0
0
3
N+N+ (NN)
0
0
0
 Cell 1 is homozygous for M, it has a “double” dose of the antigen and all
antigens on the cell for this blood group will be M. Notice the 3+
reaction.
 Cell 2 is heterozygous, a single dose of each, only 50% of the antigens
will be M and 50% will be N. Notice the 2+ reaction
 Because there are a decreased number of ANTIGENS you will expect
DECREASED serologic reactivity.
 When varying strengths of reactions are noted within a single phase of
reactivity THINK DOSAGE first and multiple antibodies second.
Anti-M
 Frequently detected as a naturally occurring saline agglutinin






at RT testing.
Most examples occur WITHOUT red cell stimulus.
Weak examples of the antibody can be enhanced by
“acidifying” the serum, lowering the pH to 6.5.
RARE examples have been found that are partly or wholly
IgG which have caused HDFN or HTR
MOST are clinically INSIGNIFICANT, no HDFN or HTR.
Do NOT need to confirm donors are M negative, must be
crossmatch compatible.
Will NOT react with enzyme treated cells.
Anti-N
 Rarely encountered.
 IgM
 Typically weakly reactive at RT
 Considered clinically insignificant although RARE examples
of IgG have been observed.
 Do NOT need to confirm donors are M negative, must be
crossmatch compatible.
 Will NOT react with enzyme treated cells.
N Typing Reagent
 Lectin extracted from Vicia graminea has specificity for N
antigen.
 Add to test RBCs as well as positive and negative controls.
 N antigen present = positive agglutination reaction.
 N antigen absent = negative agglutination reaction.
Variant MN Antigen Mg
 VERY RARE
 Person with genotype Mg N will test as M=N+ leading to
false conclusion that genotype is NN.
 Of primary importance in paternity testing.
S, s and U Antigens
 S and s produced by pair of allelic antigens at locus closely
linked to MN locus.
White
Black
S+s=U+
11%
3%
S+s+U+
44%
28%
S=s+U+
45%
69%
S=s=U=
0%
Less than 1%
Frequency of MNSs antigens
Phenotypes
M+
Blacks
(%)
74
Whites
(%)
78
N+
75
72
S+
30.5
55
s+
94
89
U+
99
99.9
High-incidence antigen
S, s and U Antibodies
 Clinically significant
 IgG
 Causes HDFN and HTR
 Will NOT react with enzyme treated cells, antigens are
destroyed by enzyme treatment.
 Must confirm that donor units are negative for antigen(s).
 Donor units must be crossmatch compatible.
U (Su)
 The U antigen is ALWAYS present when S and s are inherited
 Establish as U negative by proving they are S=s=.
 Can only give U-negative blood units found in <1% of Black
population
 Suspect anti-U when a pregnant or previously transfused
black individual reacts with ALL cells tested and has a
negative autocontrol.
 Will NOT find U negative blood in any population except the
black population.
 Two potential sources are siblings and rare donor blood.
Thought…..
 Can a person have NO MNSs antigens?
 Yes, the Mk allele produces no M, N, S, or s antigens
 Frequency of 0.00064 or .064%
Summary of MNSs Antibody Characteristics
Antibody
Anti-M
IgG Class
Clinically
significant
IgM (rare IgG)
No
Anti-N
IgM
No
Anti-S
IgG
Yes
Anti-s
IgG
Yes
Anti-U
IgG
Yes
Lutheran Blood Group System (ISBT 005)
 First example of anti-Lua was found in 1946.
 Two codominant alleles: Lua and Lub
 Antigens are poorly developed at birth.
Lutheran Antigens
Genotype
Frequency
Lu(a+b=)
0.15%
Lu (a+b+)
7.5%
Lu (a=b+)
92.35%
Lu (a=b=)
Very Rare
Anti-Lua
 Uncommon, usually naturally occurring saline agglutinin.
 Not clinically significant
 Reacts at room temperature
 RARE Mild HDN
 Naturally occurring or RARELY immune stimulated.
 May agglutinate RBCs in-vitro in MF manner which is a
characteristic helpful in identifying.
 Donors do NOT need to be antigen typed, must be crossmatch
compatible.
Anti-Lub
 Clinically significant IgG.
 Has caused MILD HDFN.
 Has been reported to cause diminished survival of transfused




RBCs (HTR).
Rare because Lub is high incidence antigen.
Finding compatible blood difficult, 99% of population is
positive.
What are two potential sources of compatible blood?
Donors must be antigen negative AND crossmatch
compatible.
Systems that Produce WarmReacting Antibodies
Kell System (ISBT 006)
 K antigen first identified in 1946 as causative antibody in case of
HDFN.
 2 major alleles (over 20 exist)
 K (Kell), <9% of population
 k (cellano), >90% of population
 The K and k genes are codominant alleles on chromosome 7 that
code for the antigens
 Well developed at birth
 The K antigen is very immunogenic (2nd to the D antigen)
in stimulating antibody production
Kell antibodies
 Produced as a result of immune stimulation.
 IgG (react well at AHG)
 Clinically significant
 Anti-K is most common because the K antigen is extremely
immunogenic
 Caused numerous cases of HTRs both immediate and delayed.
 Cause of severe HDFN.
 Anti-k occurs much less frequently due to high frequency of
antigen, <1 in 500 people are k negative.
 Donor units must be antigen negative, crossmatch compatible.
Other Kell System Antigens
 Other sets of alleles also exist in the Kell system.
 Kp antigens
 Kpa (Penney, KEL3, 1957) low frequency antigen (only 2%)
 Kpb (Rautenberg, KEL4, 1958) high frequency antigen (99.9%)
 Js antigens
 Jsa (Sutter, KEL6, 1958), 20% in Blacks, 0.1% in Whites
 Jsb (Matthews, KEL7, 1963), is high frequency 80-100%
 K is a null phenotype.
 McLeod
McLeod Syndrome
 Phenotype has weakened expression of Kell system antigens
 Associated with structural and functional abnormalities of RBCs and
leukocytes.
 Causes abnormal red cell morphologies and decreased red cell
survival:
 Acanthocytes – spur cells (defected cell membrane)
 Reticulocytes – immature red cells
 Associated with chronic granulomatous disease
 WBCs engulf microorganisms, but cannot kill (normal flora)
Other Kell System Antibodies
 Similar serologic characteristics.
 Clinically significant, immune antibodies.
 Frequency of detection influenced by
 Immunogenicity
 Distribution of antigen in population.
 Antibodies are rare which suggests low immunogenicity.
 If antigen
Kidd Blood Group
 2 antigens
 Jka and Jkb (codominant alleles)
 Show dosage
Genotype Phenotype Whites (%) Blacks (%)
JkaJka
Jk(a+b-)
26.3
51.1
JkaJkb
Jk(a+b+
50.3
40.8
JkbJkb
Jk(a-b+)
23.4
8.1
JkJk
Jk(a-b-)
rare
rare
Kidd Antigens
 Well developed at birth
 Enhanced by enzymes
 Not very accessible on the RBC membrane
Kidd antibodies
 Anti-Jka and Anti-Jkb
 IgG
 Clinically significant
 Implicated in HTR and HDN
 Common cause of delayed HTR
 Usually appears with other antibodies when detected
Kidd antibodies
 Anti-Jk3
 Found in some individuals who are Jk(a-b-)
 Far East and Pacific Islanders (RARE)
Duffy Blood Group
 Predominant genes (codominant alleles):
 Fya and Fyb code for antigens that are well developed at birth
 Antigens are destroyed by enzymes
 Show dosage
Phenotypes
Blacks
Whites
Fy(a+b-)
9
17
Fy(a+b+)
1
49
Fy(a-b+)
22
34
Fy(a-b-)
68
RARE
Duffy antibodies
 IgG
 Do not bind complement
 Clinically significant
 Stimulated by transfusion or pregnancy but not a common
cause of HDN
 Do not react with enzyme treated RBCs as antigens are
destroyed/denatured.
The Duffy and Malaria Connection
 Most African-Americans are Fy(a-b-)
 Certain malarial parasites (Plasmodium knowlesi and P. vivax)
cannot invade Fya and Fyb negative cells
 Antigen acts as a receptor for invasion and are needed for the
merozoite to attach to the red cell.
 The Fy(a-b-) phenotype is found frequently in West and
Central Africans, supporting the theory of selective evolution
Other Blood Group Antigens…
Bg Antigens
 Three (Bennett-Goodspeed) Bg antigens:
 Bga
 Bgb
 Bgc
 Related to human leukocyte antigens (HLA) on RBCs
 Antibodies are not clinically significant
Sda Antigens
 High incidence antigens found in tissues and body fluids
 Antibodies are not clinically significant
 Antibodies characteristically cause mixed field
agglutination with reagent cells
Xg Blood Group
 Only one exists (Xga)
 Inheritance occurs only on the X chromosome
 89% Xga in women
 66% in males (carry only one X)
 Men could be genotype Xga or Xg
 Women could be XgaXga, XgaXg, or XgXg
 Example: Xg(a+) male with Xg(a-) woman would only pass Xg(a+) to
daughters, but not sons
 The antigen is not a strong immunogen (not attributed to transfusion
reactions); but antibodies may be of IgG class
HTLA Antigens
 High Titer Low Avidity (HTLA)
 Occur with high frequency
 Antibodies are VERY weak and are not clinically significant
 Do not cause HDN or HTR
Review
Cold Antibodies
 IgM
 React at RT or colder
 NO HDFN or HTR
 Donor units do not need to be phenotyped for antigen.
 Donor units must be crossmatch compatible.
Cold Antibodies (IgM)
 Anti-Lea
 Anti-Leb
 Anti-I
 Anti-P1
 Anti-M
 Anti-A, -B, -H
 Anti-N
LIiPMABHN
Naturally Occurring
Cold Reacting Antibodies
Warm Antibodies
 IgG
 React at 37C and, most frequently, at AHG
 Cause of HDFN and HTR
 Donor units must be phenotyped for antigen and be antigen
negative.
 Donor units must be crossmatch compatible.
Warm antibodies (IgG)
 Rh antibodies
 Kidd
 Kell
 Duffy
 S,s
Warm Reacting Antibodies
Remember enzyme activity:
Papain, bromelin,
ficin, and trypsin
Enhanced by
enzymes
Destroyed
by enzymes
Kidd
Rh
Lewis
I
P
Fya and Fyb
M, N
S, s
Remembering Dosage:
 Kidds and Duffy the Monkey (Rh) eat lots of M&Ns
M&Ns
M&Ns
Jka, Jkb,
Kidd
Fya, Fyb,
Duffy
C, c, E, e (no D),
Rh
M, N, S, s
MNSs
adapted from Clinical Laboratory Science Review: A Bottom Line Approach (3rd Edition)
References
 Renee Wilkins, PhD, MLS(ASCP)cm University of Mississippi
Medical Center
 AABB Technical Manual, 16th edition, 2008
 Basic and Applied Concepts of Immunohematology, 2nd
edition, 2008