Immunohematology: Blood Group Systems

Immunohematology: Blood Group Systems

• Blood group systems are classified with a number and their name that is abbreviated with symbols
• Each one is determined by specific genes located on chromosomes, with CD numbers as identifiers

Glycotransferases

• Enzymes that start and lengthen glycan chains on mucins, transferring activated sugar residues
• Some blood groups are carbohydrate-based, including ABO, P1PK, Lewis, and H

Structural Relationship to Red Cells

• Some blood group systems affect the structure of red blood cells (RBCs) when present
• MNS, Diego, and Gerbich blood group systems can influence the shape of RBCs

Transport Proteins

• Some systems function as transport proteins
• Rh, Kidd, Diego, Colton, and Kx blood group systems are involved in transportation

Complement Pathway Molecules

• Several blood group systems play a role in the complement pathway
• Chido/Rodgers, Cromer, and Knops blood group systems participate in this pathway

Adhesion Molecules

• Some blood groups are adhesion molecules
• Lutheran, Xg, Landsteiner-Wiener, and Indian blood group systems act in adhesion

Microbial and Biological Receptors

• MNS, Duffy, P, Lewis, and Cromer blood group systems can act as microbial receptors
• Duffy, Knops, and Indian blood group system act as biological receptors
• Lewis BGS increases susceptibility to H. pylori infections, which can cause ulcers

Key facts about Lewis Blood Group antibodies

• Named after the first person to make the antibody
• Anti-Lea and Anti-Leb are IgM antibodies with no clinical significance

IgM antibodies

• These antibodies haven't been linked to HDFN because placentas keep antibodies from crossing, and antigens aren't well-formed at birth
• IgM is efficient in complement binding

Genetics of Lewis Blood Group

• Lewis (Le, FUT3) gene is on chromosome 19 at 19p13.3
• Secretor (Se, FUT2) gene is on chromosome 19 at 19q13.3

Role of Secretor Gene

• Influences Lewis blood group production not only on blood group antigens
• Manufactured by tissue cells and secreted into body fluids
• Manifests ABO blood groups in body fluids

Lewis Locus Alleles

• Two alleles make up Lewis locus, these are Le and le , secretor locus is made up of Se and se
• Le gene produces Lea
• Se gene produces Leb

Lewis Glycolipids

• Can't be detected in plasma until around 10 days after birth
• Lewis blood group is antithetical, this mean single genes code pairs and occasionally more than one pair of antigens

Lewis Antigens

• Not on cord RBCs, often reduced on mother's RBCs during pregnancy
• Can't be transferred to the baby because of IgM
• Present in lymphocytes, platelets, and other tissues like the pancreas
• Resistant to ficin, papain, DTT, and glycine acid EDTA enzyme treatments

Lewis Phenotypes

• A person can still secrete Lea, event if they're a nonsecretor (sese)
• Not intrinsic to RBCs but adsorbed onto RBC membranes from plasma
• Cord blood and RBCs from newborns show Le (a-b-) phenotype

Key Facts regarding antigens

• Present/Absent in secretors based on genes
• Red cells only adsorb glycolipids

Lewis genes and Red Cell Phenotypes

• Le, Se, and A/B/H antigens are responsible for: Lea, Leb, A, B, H in secretions and A, B, H, Le(a – b+) on red cells
• lele, Se, and A/B/H antigens are responsible for: A, B, Η secretion and A, B, H, Le(a – b –) on red cells
• Le, and sese, antigens are responsible for: Lea secretions and A, B, H, Le(a+b –) on red cells
• lele, and sese antigens are responsible for: no secretions and A, B, H, Le(a – b –) on red cells
• Le, and sese hh, A/B antigens are responsible for: Lea secretions and Oh, Le(a+b –) on red cells
• Le, Se, hh, and A/B antigens are responsible for: Lea, Leb, A, B, Η secretions and A*, B*, Le(a – b+) on red cells

Red Cell Phenotypes

• From the Inheritance of Le, Se, and H genes giving: Le (a-b+)
• From inheritance of Le and sese genes giving: Le (a+b -), these persist throughout life if lele follows
• The transformation to Leb phenotype after birth is Le(a–b–) to Le(a+b–) to Le(a+b+) to Le(a–b+)

Pregnancy Changes

• Lewis antigens change pregnancy by decreasing both Lea and Leb

Type 1 Chain

• Has terminal galactose in a 1-3 linkage to subterminal N-acetylglucosamine

Best description for Lewis antigens

• Lea and Leb are not antithetical antigens

If all tests are negative:

• Which of the following genotypes would explain RBCs typed as group A Le(a+b–)?
• A/O Lele HH Sese

Anti-LebH reactivity

• Anti-LebH will not react or will react more weakly with Group O Le(b+)

The P blood group system includes

• P1PK and Globeside Systems and Related Antigens

P1 and Pk antigen facts

• Introduced in 1927 by Landsteiner and Levine
• Matson and coworkers first documented Pk antigen

Matson and coworkers identified Pk - traditionally

• Comprised of the P, P1 and Pk antigens and later, Luke (LKE).

Current ISBT nomenclature:

• P1 and Pk are assigned to the P1Pk blood group system (003, P1PK)
• P is assigned to the globoside blood group system (028, symbol GLOB)
• LKE and PX2 are assigned to the Globoside Collection (029, GLOB)
• *Genetics- P1PK gene (at chromosome 22q11.2) and P gene (at chromosome 3q26.1)

Biosynthetic Pathways of the P blood group antigens

• Common Precursor: Lactosylceramide (Gb2), also known as ceramide dihexose or CDH
• Paragloboside is also the type 2 precursor for ABH

Antigens

• P1, P, or Pk are found on RBCs, lymphocytes, granulocytes, and monocytes
• P can be found on platelets, epithelial cells, and fibroblasts
• P and Pk have been found in plasma as glycosphingolipids and as glycoproteins in hydatid cyst fluid

All cells are targeted.

• The antigens have not been identified in secretions

P1 Antigen characteristics

• Poorly expressed at birth and may take up to 7 years to be fully expressed
• It deteriorates rapidly on storage.
• Blacks have stronger expression of P1 than whites

All P antibody categories:

Clinically Insignificant → IgM, and Potently Hemolytic → Ig1 & IgG3

• Common, naturally occurring IgM antibody in the sera of P (-) individuals
• Typically weak, cold reactive saline agglutinin optimally reactive at 4 degrees Celsius and not seen in routine testing

Disease associations with P Antibodies:

• Parasitic infections
• Anti – P1 in P1 individuals are infected with tapeworms, hydatid moles, and liver diseases
• Potential to cause severe immediate and delayed HTR and HDFN
• Associated with parasitic infections
• P antigen has connections to Auto, Allo, all individuals of each animal

More information regarding Auto, Allo, and other P antibodies:

• Autoanti-P: The IgG autoantibody in (PCH), biphasic hemolysin being demonstrated, both in the cold and warm
• Allo Anti – P: forms antibody against different individual but same species, seen but very significant in transfusion, associated with early abortions, and is IgG

Luke Antigen is (LKE):

• Described by Tippett and colleagues in 1965 in the serum of a patient with Hodgkin’s Lymphoma

Tippetts Luke key notes

• The antigen has 3 phenotypes, 80% being Luke+, 14% Lule (w), 2% Luke-, and all individuals with the p/Pk phenotype

Disease

• There are parasitic symptoms, early abortions, and or Autoanticities depending with each situation

Blood Groups that will have P, and what group has HIV protections:

• Autoanti-P, Anti-PP1Pk P1 = (fascioliasis) P2 = (1/3 PP1) P. = (auto) P1k , And P2k,

• They are located within the human or the bloodstream
  

Autoanticities: Are the key for parasitic infections associated with each situation (auto) and have HIV protections due to HIV

PRACTICE: MNTs

Most antibodies will be cold/warm or the situation that occurs

1. Paroxysmal cold ( Anti – P)
2. M pneumonia (I or i)
3. Fasciolisis Anti-P2 antibody
4. Antill antibodies don't react in adults because “adult i has a weak reaction” *adult test
5. What recognizes the auto of autoanti-P antigen?
6. Shiga toxins for p antagists, which causes HUSS

The I and i Blood Group System

Antigens associated with this system have these characteristics:

• Have i and individuals ,with most being I
• During the first 18 months the quantity of I slowly increases
• Infant RBCs are rich in i, Adult red blood cells are rich with I

IT Antigen/Antibody facts:

• Recognizes transition states/examples occur by the IgM and IgG and/or WAIHA patients = 37oC

Anti - 1 testable situations:

• testing at to locate reactivity
• The tests for testing the reactivity is to test if there will be testing for both situations* Cannot bind as its an IgG-M, meaning they won't bind because of poor expression . Is not associated with -Antibodies that aren't Anti- I 1 Auto, 2 -j- 3-H

Testing conditions (All of these)

   Is a common autoantibody ,test 4oC/enzyme

What are All the statements of Allo

• It means there's a never been descirbet, the patient does not develop anti-i , and if they potent = infections. -Associated with HEMPS and EBV

M&N Antigen facts:

• There are 46 antigen -making it same size RH

•   What are the 4: MNSsU
  

•   U= (univeral) has high prevalance for antibodies
  

• What are GPBs, and GPAs? (glycophorin M s S) GPA Is associated with theronon and glycine (Serine And Lucine are also possible, and glutamine) The M: Serine Serine Threonine Threonine Glycine- The N: Licine Serine Threonine Threonine Glutamic acid -

All M &N antigens must be this:

• What effects all the antigens: MNOs and U
• They decrease by enzymes 1: if there is no class= antiM, it cannot be tested.

MN antibody functions

• It does not help patients with hemoglobin. It only inhibits. -Particularly A child A patient has bacteria Can't perform reactions because enzyme treatment No complement binding because it is usually from M What are U phenotype?
• has the ability to bind It will make sure lower urinary traction occurs What inhibits the urinary tract? - Uti- coli What creates or decreases plasmodium’s from the immune system? MNO And if found increased, this also increases the chance M and N , AND s_

PRACTICE TIME again:

• Which of the following statements are TRUE for M or N and 1:They are all 2: if 1,2,3 or more
• Which of the following is the most descriptive for MN antibodies?
• (B =they aren't developed or reactive
• anti U will not react with M AND L And the s antigens have different positions, usually positions from 2-9. They’re at 2-8, AND 9