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Importance of the other blood group systems

You are here : Home/ Blood Bank Zone/ Principles of Immunohaematology/ 9. Importance of the other blood group systems

9. Importance of the other blood group systems

Blood samples are routinely grouped for ABO & Rh only. However all individuals carry antigens from other blood group systems also and they may also develop antibodies if transfused blood containing antigens absent on their own RBCs.

All patient samples are subjected to an antibody screen prior to a transfusion to detect such unexpected antibodies. If the antibody screen is positive, it is necessary to identify the antibody and transfuse blood lacking the corresponding antigen.

Lewis blood group system

Lewis antigens (Lea and Leh) derived from precursor and H substances involved in synthesis of A and B antigens are absorbed by red cells from plasma. Le gene is present on chromosome 19 and is inherited independent of ABO, hh and Sese genes. The phenotypic expression of Le gene depends on individual’s Se/se and H/h status. All Le (a-b+) are secretors and all Le(a+b-) are non-secretors. Le (ab-) individuals can be secretors or non-secretors.

Lewis antibodies

Lewis antibodies are usually naturally acquired IgM type. They fix compliment and may cause haemolysis generally below room temperature. Anti-Lea antibodies commonly occur in Le (a-b-) individuals and rarely in Le (a-b+) individuals. Both anti-Lea and -Leh can cause decreased red cell survival and HTR. In pregnancy, Lewis antibodies (IgM) are found however, these do not cause HDNB.

MNSs blood group system

Two groups of antigens MN and Ss U are situated on glycophorin A and glycophorin B respectively. Two pairs of codominant genes M&N, S and s located on chromosome 4, control the expression of these antigens.

MN antigens

Red cells express M,N or both antigens in addition to “N-like” antigen on M cells.
Phenotypes Genotypes

The homozygous individuals show stronger agglutination than heterozygotes thus showing a dosage effect. The actively of the antigens depends on presence and composition of attached sialic acid residue. Therefore, the activity of these antigens is destroyed after treatment with proteolytic enzymes.

SsU antigens

Ss antigen are located on sialoglycoprotein, glycophorin B and U antigen is related to all genes involved in the synthesis of Ss gene products.

MN antibodies

Anti-M is a naturally occurring antibody and is found more commonly than anti-N. MN antibodies do not usually cause transfusion-induced reactions as MN antigens are weak immunogens. Anti-Mantibodies usually are IgG which behave as “complete” antibodies because of increased density of antigenic sites on red cells. These are cold antibodies.

Anti-N antibody, although uncommon is also a cold antibody of IgM type.

Anti-M and anti-N are not usually clinically significant but HDN and HTR are known to occur.
Ss antibodies

Anti-S and anti-s are clinically significant antibodies. These are formed in response to prior blood transfusion and may be either IgM or IgG type. Anti-s is less frequently encountered antibody than antiS. Anti-U antibodies are found in S-s-U- individuals and may cause HTR.

Kell blood group system

Kell antigens are highly immunogenic and known to cause HTR and HDN. Two antigens K (Ki) and K (1(2) have been identified. Incidence of Kell antigen (K) in India is reported to be 0.3-0.7%, where as cellano (k) is a high frequency antigen (>99% incidence). Kpa (K3), Kph (1(4), Jsa (K6) and Jsb (1(7) are other antigens of this system consisting of 23 KelI antigens. In Ko (Kell null), all Kell system antigens are absent.
As the Kell system consists of numerous antigens, it has become very complex and now a numerical nomenclature has been introduced.

Mcleod phenotype

Kell antigens are expressed weakly in this X-lkinked syndrome consisting of mild haemolytic anaemia, acanthocytosis, neuomuscular abnormalities with elevated cratine phosphokinase (CPK) enzyme.
Individuals with Mcleod phenotype may have chronic granulomatous disease (CGD), or a high level of CPK.

Kell antibodies

Anti-K are formed in response to transfusion and are usually IgG type. Alloimmunization in mother can occur due to foetomaternal haemorrhage. Anti-K can cause immediate and delayed haemolytic reactions. Anti-k (anti-cellano) is less common and only KK homozygotes produce this antibody after blood transfusion.

These antibodies are best detected by the indirect antiglobulin test. Some examples do bind complement also.

The in-vitro characteristics of anti-Kell antibody
  • Best detected by the antiglobulin test
  • Occasionally reacts in saline
  • May react at room temperature or lower
  • Does not typically show dosage effect
  • Reactions are not inhibited by enzyme treatment of redcells

Duffy antigen system

Duffy antigen system consists of two antigens Fya (FYI) and Fyb (FY2). The alleles of Duffy antigens are located on chromosome I. The incidence of Fya is very high in Asians and Fya with anti-Fya poses a major problem in clinical transfusion practice. Plasmodium vivax (malaria) infection does not affect red cells lacking Fya and Fyb as these act as receptors on red cell membrane for invasion by vivax merozoites. P. falciparum infection is not associated with Duffy phenotype.

Four different types of phenotype are defined Fy(a+b+), Fy (a+b-), Fy (a-b+) and Fy (a-b-) in decreasing order of frequency. Duffy antigens are thermolabile and are inactivated by heating at 56°C for 10 minutes. Enzymes markedly reduce the activity of Fya & Fyb.

Duffy antibodies are usually of IgG type and bind with complement to produce transfusion reactions. Anti-Fy2 is the most frequent antibody induced by red cell exposure which may cause delayed haemolytic transfusion reactions. Fyb antigen is a weak antigen and anti-Fyb is a rare antibody.

The Duffy antibodies are detectable only by indirect antiglobulin test and antibody reacts more strongly with homozygous cells as compared to heterozygous cells.

The activity is enhanced by LISS and reduced pH of the suspending media. Both anti-Fya and anti-Fyb are known to cause HTR and HDN.

Kldd blood group system

Two antigens Jka and Jkb (JK2) are controlled by genes present on chromosome 18. Three common phenotypes are Jk (a+b+), Jk (a+b-) and .Jk (a-b+). The phenotype Jk (a-b-) is very rare. These antigens are immunologically weak but are significant in clinical practice. JUdd antibodies are immune in nature and found in low titre for short duration after antigen stimulation. These antibodies may be either IgG or IgM which can bind complement and are detected by the antiglobulin test using polyspecific anti-human globulin. These may lead to delayed haemolytic transfusion reactions:

Lutheran blood group system

Two common antigens Lua (Lul) and Lub (Lu2) are controlled by Lutheran gene located on chromosome 19 which is linked to secretor gene. Lu antigens are present at birth. Most common phenotypes are Lu (a-b+), Lu (a+b+) and Lu (a+b-). Lu (a-b-) phenotype is rarely encountered. The incidence for lua antigen in India is 1: 200 and Luh is a high frequency antigen.

Lutheran antibodies are uncommon and occur in low titre. Anti-Lua may be IgG or IgM type which and not cause significant haemolytic transfusion reaction. It could be naturally occurring or produced by immunization.

Anti-Lub is a rare antibody which reduced the survival of transfused red cells, is reported to IgA in nature and may cause delayed transfusion reactions. These are found in Lu (a-b-) individuals following blood transfusion or pregnancy.

Anti-Lub is best detected by the antiglobulin test.

P blood group system

Individuals lacking P1 antigen but show to possess P antigen are called as P2 (P+P1-). All individuals are either P1 or P2 and complexities of P group are explained on similar basis are subgroups of A into Al and A2. Anti-P1 is found in normal individuals with P2 phenotype and is active at 37°C. It does not cause clinically significant haemolytic reaction. Anti-P is the major antibody in P1k and P2k phenotypes and can cause haemolytic transfusion reactions.

Anti-PP1Pk (anti-Tja) is found in individuals with p phenotype and is usually (IgM types). This may cause haemolytic transfusion reaction and its presence increases the risk of abortion in pregnant mothers. Neutralization of anti-P with P substance (present in hydatid cyst fluid) helps confirm the specificity of the antibody.

Auto anti-P is found in the serum of the patients of paroxysmal cold haemoglobinuria.

Ii antigens

I antigen is present on the red cells in adults in varying strength and is expressed weakly on cord blood cells. The i antigen is expressed strongly on cord blood cells and in neonatal red cells. The expression of i antigen decreases with age as the I antigen increases during first 18 months of age.
I specific antibodies

Anti-I antibodies are IgM type and present in low titres in all individuals. The naturally occurring antibody is active at cold temperature and is not clinically significant. Anti-i may be found in patients suffering from lymphoma or infectious mononucleosis.

Many other blood group systems have been described such as Xg, Ina, Bg, Diego (Di), cartwright (Yt),chido (Ch) and Roger (Rg), etc.

High frequency antigens (Public antigens)

Antigens with a frequency of >99% on human red cells e.g. Kph,Jsh, Lub, k, vel, Ge, etc.
Low frequency antigens (private antigens)

Antigens with a frequency of <1% of human red cells e.g. SW9,Js9,Kpa etc.

Blood bank zone Next Articles
  1. Introduction
  2. Immunohaematology Reactions
  3. Reagents Used In Detecting Antigen-Antibody Reactions
  4. Factors Influencing Antigen-Antibody Reaction
  5. Complement System
  6. Genetics
  7. Blood Group Systems
  8. Blood Genetics & Biochemistry
  9. Importance of the other blood group systems
  10. Red Cell Serology
You are here : Home/ Blood Bank Zone/ Principles of Immunohaematology/ 9. Importance of the other blood group systems

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