OTHER BLOOD GROUPS SYSTEM

Cold Antibodies (IgM) Warm Antibodies (IgG)

 Anti-Lea  Rh antibodies
 Anti-Leb  Kell
 Anti-I  Duffy
 Anti-P1  Kidd
 Anti-M
 S,s
 Anti-A, -B, -H
 Anti-N
ENZYME ACTIVITY (papain, bromelin, ficin and trypsin)
Enhanced by Enzymes Destroyed by Enzymes
 Kidd  Fya and Fyb
 Rh  M, N
 Lewis  S, s
 I
 P

SYTEMS THAT PRODUCE COLD-REACTING ANTIBODIES

Lewis Antigens
Soluble antigens produced by tissues and found in
body fluids (plasma)

 Adsorbed on the RBC

Lewis Inheritance

 Lewis system depends on Hh, Se, and Le genes

 le, h, and se do not produce products
 If the Le gene is inherited, Lea substance is produced
 Le, H, and Se genes must ALL be inherited to convert Lea to Leb.
Examples:

Lewis Antibodies

 Usually occur naturally in those who are Le(a-b-)

 Other phenotypes RARELY produce the antibody
 IgM (may fix complement, becoming hemolytic)
 Enzymes enhance activity
 May be detected soon after pregnancy because pregnant women may temporarily become Le(a-b-)
 No clinical significance…Why?
  Le antibodies in a patient can be neutralized by the Lewis antigens in the donor’s plasma (cancel each
other out)
 do not cause HDN because they do not cross placenta (antigens not developed well in cord blood)
Le(a-b-)
I Antigens

 These antigens may be I or i

 They form on the precursor chain of RBC
 Newborns have i antigen
 Adults have I antigen
 i antigen (linear) converts to I (branched) as the child matures (precursor chain is more linear at birth)
at about 18 months

I Antibodies

 Most people have autoanti-I (RT or 4°C)

 Alloanti-I is very rare
 Cold-reacting (RT or below) IgM antibody
 Clinically insignificant
 Can attach complement (no hemolysis unless it reacts at 37°)
 Prewarming the tests can eliminate reactivity
 Enzymes can enhance detection
 Anti-I often occurs as anti-IH
 This means it will react at different strengths with reagent cells (depending on the amount of H antigen
on the RBC)
 O cells would have a strong reaction
 A cells would have a weaker reaction
Anti-I Antibodies

 Anti-I:
- Associated as a cause of Cold Agglutinin Disease (similar to PCH)
- May be secondary to Mycoplasma pneumoniae infections
 Anti-i:
- rare and is sometimes associated with infectious mononucleosis
P Antigen

 Similar to the ABO system

 The most common phenotypes are P1 and P2
 P1 – consists of P1 and P antigens
 P2 – consists of only P antigens
 Like the A2 subgroup, P2 groups can produce anti-P1
 75% of adults have P1
P1 Antigen

 Strength of the antigen decreases upon storage

 Found in secretions like plasma and hydatid cyst fluid
- Cyst of a dog tapeworm
P Antibodies

 Anti-P1
- Naturally occurring IgM
- Not clinically significant
- Can be neutralized by hydatid cyst fluid to reveal more clinically significant antibodies
 Anti-P
- Produced in individuals with paroxysmal cold hemoglobinuria (PCH)
- PCH – IgG auto-anti-P attaches complement when cold (fingers, toes). As the red cells circulate,
they begin to lyse (releasing Hgb)
 - This PCH antibody is also called the Donath- Landsteiner antibody

MNSs BLOOD SYSTEM

 4 important antigens (more exist):

I. M
II. N
III. S
IV. s
V. U (ALWAYS present when S & s are
inherited)
 M & N located on Glycophorin A
 S & s and U located on Glycophorin B
 Remember: Glycophorin is a protein that carries
many RBC antigens

MNSs Antigens

 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)
U (Su) Antigen

 The U antigen is ALWAYS present when S & s are inherited

 About 85% of S-s- individuals are U- negative (RARE)
 U-negative cells are only found in the Black population
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%

Anti-M and Anti-N Antibodies

 Demonstrate dosage
 Anti-M and anti-N
- IgM (rarely IgG)
- Clinically insignificant
- If IgG, could be implicated in HDN (RARE)
- Will not react with enzyme treated cells

Anti-S, Anti-s, and Anti-U

 Clinically significant
 IgG
 Can cause RBC destruction and HDN
 Anti-U
- will react with S+ or s+ red cells
- Usually occurs in S-s- cells
- Can only give U-negative blood units found in <1% of Black population
- Contact rare donor registry
 SYSTEMS THAT PRODUCE WARM-REACTING ANTIBODIES

KELL SYSTEM

 Similar to the Rh system

 2 major antigens (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
Other Kell Antigens

 Other sets of alleles also exist in the Kell system:

 Analogous to the Rh system: C/c and E/e
 Kp antigens
- Kpa is a low frequency antigen (only 2%)
- Kpb is a high frequency antigen (99.9%)
 Js antigens
- Jsa (20% in Blacks, 0.1% in Whites)
- Jsb is high frequency (80-100%)
Kell Antigens

 Kell antigens have disulfide-bonded regions on the glycoproteins

 This makes them sensitive to sulfhydryl reagents:
 2-mercaptoethanol (2-ME)
 Dithiothreitol (DTT)
 2-aminoethylisothiouronium bromide (AET)

Kellnull or K0

 No expression of Kell antigens except a related antigen called Kx

 As a result of transfusion, K0 individuals can develop anti-Ku (Ku is on RBCs that have Kell antigens)
 Rare Kell negative units should be given
Kell antibodies

 IgG (react well at AHG)

 Produced as a result of immune stimulation (transfusion, pregnancy)
 Clinically significant
 Anti-K is most common because the K antigen is extremely immunogenic
 k, Kpb, and Jsb antibodies are rare (many individuals have these antigens and won’t develop an antibody)
 The other antibodies are also rare since few donors have the antigen
Kx Antigen

 Not a part of the Kell system, but is related

- Kx antigens are present in small amounts in individuals with normal Kell antigens
- Kx antigens are increased in those who are K0
McLeod Syndrome

 The XK1 gene (on the X chromosome) codes for the Kx antigen
 When the gene is not inherited, Kx is absent (almost exclusive in White males)
 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)
 KIDD BLOOD GROUP

 2 antigens
 Jka and Jkb (codominant alleles)
 Show dosage
Kidd Antigens

 Well developed at birth

 Enhanced by enzymes
 Not very acessible 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
 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

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
The Duffy and Malaria Connection

 Most African-Americans are Fy(a-b-)

 Interestingly, certain malarial parasites (Plasmodium knowlesi and P. vivax) will not invade Fy a and
Fyb negative cells
 It seems either Fya or Fyb 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

Lutheran Blood Group System

 2 codominant alleles: Lua and Lub

 Weakly expressed on cord blood cells
 Most individuals (92%) have the Lub antigen, Lu(a-b+)
 The Lu(a-b-) phenotype is RARE
Lutheran Antibodies

 Anti-Lua
- IgM and IgG
- Not clinically significant
- Reacts at room temperature
 - Mild HDN
- Naturally occurring or immune stimulated
 Anti-Lub
- Rare because Lub is high incidence antigen
- IgG
- Associated with transfusion reactions (rare HDN)
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

CARTWRIGHT

 Yta is a common antigen in Black and White population.

 Ytb is 8%, an allele of Yta
 Anti Yta is uncommon found in persons with history of pregnancy

COLTON

 COa is 99.8%
 Blacks have lower resistance
 Anti COa and Anti Cob are IgG
 Anti COa causes HTR and HDN
 Anti Cob is found in HTR

DOMROCK

 Abtigens ( DOa an DOb)

 DO(b+) = 83% of White
 Anti DOa is associated with HTR
DIEGO

 Dia: Whites are 100% Dia-

 Dib: Whites are 100% Dib+
 Anti Dia reacts at room temp at 37 deg.C and AHG
 Anti Dia and Anti Dib are implicated in HTR and HDN

SCIANNA

 Sc1: high frequency antigen

 Sc2: low frequency antigen
 Anti Sc1 and Anti Sc2 are uncommon
 Implicated in TR and HDN

HLA

 They are antibodies that were contaminants of many typing sera

 Found in multiparous women often with isoleukoagglutinins
 Destroyed by bromelin
 detected with fresh erythrocytes collected into ACD
 Corresponding antigens
- Bga and Bgb with Bennett GoodSpeed Group
- Bgc
- In l969: the erythrocytes Bga was correlated to HLA B7, first antigen on erythrocytes B17 and BGc as
HLA 28 was reported
- Most if not all, HLA antigens are present on the erythrocytes of individuals possessing the antigen on
leukocytes.
- Bg or HLA antibodies maybe detected in multiparous or multitransfused patients.

MATURE GRANULOCYTES

 Human Granulocyte antigens (HGA-3a3a)

- NA1 and NA2…. NB1 and NB2…NC1 ND1…NE1
- Associated to febrile transfusion reactions.
WRIGHT

 Wra is only 2 in 1000 samples

 Anti Wra is a frequently occurring antibody. It can be detected in 1:100 persons
 Found in serum of patients who have formed other blood group antibodies and in serum of patients with
autoimmune hemolytic anemia.

PLATELET ANTIGENS

 HPA 1 to HPA 5
- HPA 1 and HPA4- glycoprotein 111a
- HPA 5. . . . . . . . .glycoprotein Ia
- HPA 2 . . . . . . . . Glycoprotein IB
- HPA 3 . . . . . . . . Glycoprotein IIB
 Testing for platelet antibodies can be useful as an adjunct to HLA matching in selecting compatible
platelets.
 Platelets express varying amounts of HLA-A and HLA-B but not HLA-D and DR
OTHER RED BLOOD CELL ANTIGENS

 Yka : York
 Csa : Cost Sterling
 Kna : Knops Heleson
 McCa : MacCoy
 Cha : Chido
 Rga : Rodger
 JMH : John Milton Hagen
 Gya and Hy: Holley and Gregory

The antibodies are reactive in AHG phase of testing.

 Ata ( Augustine)
 Cra (Cromer)
 Ge (Gerbich)
 Gya (Gregory)
 Hy (Holley)
 Jra (Jacobs)
 Joa (Joseph)
 Lan (Langeries)