1bb. mlt309. 2013-2014.lec.6.mr. waggas. other blood group systems

1BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

Other Blood Group Systems

Introduction For each blood group system you MUST

know: Antigen development, if important. Antibody class usually involved. Phase of reactivity in in-vitro tests. Clinical significance. Whether donor units must be antigen negative. Any unique characteristics of the blood group

antigens and/or antibodies.


Major Blood Group Systems Lewis I P MNSs Kell Kidd Duffy


Systems that Produce Cold-

Reacting Antibodies

Lewis System (ISBT 007) Major antigens Lea and Leb , they are

glycoproteins Antigens ARE NOT intrinsic to RBCs but

are absorbed from the plasma and inserted into RBC membrane.

Genetic control reside in single gene “Le” Amorph le, if homozygous will not have Lewis

antigens Lea formed first, then modified to form Leb

Lewis phenotype of RBC can be changed by incubating with plasma containing Lea or Leb glycoplipid.


Lewis System Lewis antigens in infants

Antigens absent or extremely weak at birth Expression of Leb is gradual

Birth Le (a-b-) 2 months Le(a+b-) 12 to 18 months Le(a+b+) 2 to 3 years Le (a-b+)

Lewis antigens cannot be used for paternity testing on infants. Why?


Lewis Antigens and Pregnancy Antigen strength may decline dramatically

during pregnancy. Transiently Le (a-b-) may produce Lewis

antibodies during pregnancy. Antigens return after delivery and

antibodies disappear.


Interaction of Le, Se and H Genes The le, h and se genes are amorphs and

produce no detectable products. lele will not have Lewis antigens, but if Se

present will have A, B and H in secretions Genotype se/se and have one Lewis gene

will have Lea in their secretions but no A, B or H.


Lewis Antibodies Naturally occurring, NOT clinically significant Almost always IgM

React most often at RT Agglutination relatively fragile, easily dispersed May cause ABO discrepancy if reverse cells

have Lewis antigen. Occur almost exclusively in Le (a-b-) and

production of anti-Lea AND –Leb not unusual Anti-Lea frequently encountered, anti-Leb rarely

encountered.


Lewis Antibodies Although most react at RT reactivity may be

seen at 37C, but is weaker and may be weakly reactive at AHG

Can bind complement and cause IN-VITRO hemolysis, most often with enzyme treated cells

Antibodies NOT implicated in HDFN – TWO REASONS

Antibodies are IgM and Antigens are poorly developed at birth


I Blood Group (ISBT 027) Antigens are I or I Newborns have i antigen Adults have I antigen i antigen converts to I as the child matures

at about 18 months


I antibodies Are IgM, naturally occurring auto-

agglutinins with low thermal range. They are not clinically significant unless

they react above 30oC. Can attach complement (no hemolysis unless it

reacts at 37°) Enzymes can enhance detection


I antibodies 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 reactionRemember : strength of H sub. : O > A2 > A2B > B > A1 > A1B.


Anti-I antibodies Anti-I:

Associated as a cause of Cold Agglutinin Disease

May be secondary to Mycoplasma pneumoniae infections

Anti-i: rare and is sometimes associated with

infectious mononucleosis


P Blood Group (ISBT 003) 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

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):

M N S s U (ALWAYS present when S & s are inherited)

M & N located on Glycophorin A S & s and U located on Glycophorin BRemember: Glycophorin is a protein that carries many RBC antigens


MNSs Antigens

RBC

Glycophorin A

Glycophorin B

M

N

SsU

M & N only differ in their amino acid

sequence at positions 1 and 5

S & s only differ in their amino acid

sequence at position 29

….5, 4, 3, 2, 1 (NH2 end)COOH end ….. 20

MNSs antigens Antigens are destroyed by enzymes (i.e.

ficin, papain) 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


Frequency of MNSs antigens

Phenotypes Blacks (%) Whites (%)

M+ 74 78

N+ 75 72

S+ 30.5 55

s+ 94 89

U+ 99 99.9

High-incidence antigen22

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

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


MNSs Antibody Characteristics

Antibody IgG Class Clinically significant

Anti-M IgM (rare IgG) No

Anti-N IgM No

Anti-S IgG Yes

Anti-s IgG Yes

Anti-U IgG Yes


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


Kell antigens Kell antigens have disulfide-bonded

regions on the glycoproteins This makes them sensitive to sulfhydryl

reagents: 2-mercaptoethanol (2-ME) Dithiothreitol (DTT) So Kell system Ags are easily inactivated by

treating RBCs with these substances.


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


Kidd Blood Group 2 antigens

Jka and Jkb (codominant alleles)

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


Duffy Blood Group Predominant genes (codominant alleles):

Fya and Fyb code for antigens that are well developed at birth

Antigens are destroyed by enzymes

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


The Duffy and Malaria Connection Most African-Americans are Fy(a-b-) Interestingly, certain malarial parasites

(Plasmodium knowlesi and P. vivax) will not invade Fya 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)


Cold Antibodies (IgM) Anti-Lea

Anti-Leb

Anti-I Anti-P1 Anti-M Anti-A, -B, -H Anti-N

LIiPMABHNNaturally Occurring 41BB. MLT309. 2013-2014.Lec.6.Mr. Waggas

Warm antibodies (IgG)

Rh Kell Duffy Kidd S,s U


Remember enzyme activity:

Enhanced by enzymes

Destroyed by enzymes

KiddRh

LewisIP

Fya and Fyb M, NS, s

Papain, bromelin, ficin, and trypsin


Thanks


1bb. mlt309. 2013-2014.lec.6.mr. waggas. other blood group systems

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