Lecture 17: Blood group serology

Question 1

What are Blood group antigens?

Answer 1

• Glycoproteins and glycolipids present on the surfae of red cells. Some eg. ABO, may also be present more widely on endothelial surfaces
• Genetically determined (generally autosomal and co-dominant)
• Limited understanding of biological function of the antigens

Question 2

Genetic control of blood groups?

Answer 2

• Protein determinants - gene codes for the antigenic determinant itself (Rh, Kell, Kidd systems)
• Glycolipid determinants - gene codes for production of enzyme that add or remove carbohydrates or lipids (ABO, lewis group systems)

Question 3

Functional Aspects of Blood group antigens?

Answer 3

Duffy blood group system

• Duffy antigen acts as the entry point to the red cell for malaria
• In caucasian pop. Fy^a-Fyb phenotype is rare
• In african americans upto 40% have this natural resistance gene

The McLeod Phenotye

• Kx null phenotype associated with chronic granulomatous disease and acanthocytosis.

Question 4

Clinical importance of blood group antibodies? Two types

Answer 4

Blood group systems are important because of their ability to stimulate antibody production and recognise ‘foreign’ antigens

May be IgM, IgG, IgA

Naturally occurring - usually glycolipid antigen and can activate complement (no exposure to foreign red cells required but rather exposure to bacteria containing similar antigens - cross reacting. Not present at birth and are mostly IgM with some IgG. ABO and Lewis antigens fall in this category)

Immune stimulated - Usually glycoprotein antigen and most can’t activate complement (Exposure to foreign red cells required. Eg transfusion or pregnancy. Tend to be IgG)

Question 5

ABO Antigens? what do ya know?

Answer 5

They are widely distributed on blood cells, epithelial cells and bodily fluids.

The phenotype is determined by a series of glycosyltransferase enzymes that are responsible for the addition of CHO molecules to the basic membrane structure

The H antigen is necessary for the ABO phenotype to be expressed. (nothing added is type O)

Question 6

Clinical relevance of ABO system?

Answer 6

• ABO antibodies are naturally occuring and appear between 3-6months of age.
• Transfusion errors can be fatal or through activation of the complement system lead to intravascular hemolysis, renal failure or DIC

Question 7

Rh Blood group system?

Answer 7

Second most important blood group system

• Protein determinant
• Expressed on only red blood cells with Antibodies produced following immune stimulation
• Highly immunogenic, particularly Rh(D)
• d antigen is an amorph and makes no difference to the cell

Question 8

Clinical importance of Rh(D) in transfusions?

Answer 8

• 90% of Rh(D) negative individuals will produce anti-D if transfused with Rh(D) positive red cells.
• This IgG is unable to bind complement and red cell destruction is extravascular
• Anti-D is the most common cause of Haemolytic Disease of the newborn (never transfuse Rh(D) positive into an Rh(D) negative female of childbearing age)

Question 9

The expanded Rh system consists of?

Answer 9

Rh antigen is the production of three genetically closely linked alleles. Wether or not it is clinically relevant is unknown.

The principal production of the allelic pairs are:

• C and c
• D and d (d is an amorph)
• E and e

Its very complex and when looking for donors it must be fully understood and worked out.

Question 10

Minor blood group systems?

Answer 10

Kell = K(Kell) and k(cellano)

Kidd = Jka and Jkb

Duffy = Fya and Fyb

Question 11

Agglutination of RBC with IgG and IgM?

Answer 11

IgM moleculaes are larger that the negative so called zeta potential that holds the RBC apart and so therefore can produce cross linking leading to agglutination.

IgG molecules are too small to produce cross-linking and hence a potentiator is needed to produce agglutination (most frequently Anti-human globulin or other enzymes)

Question 12

Haemolytic disease of the Newborn?

Answer 12

• Occurs when maternal antibody crosses placenta resulting in destruction of foetal red cells
• Always involves an IgG antibody
• Most frequently caused by presence of anti-D, followed by antic and anti-Kell
• Frequency greatly reduced by introduction of immunoprophylaxis
• 67% of babies born to a Rh(D) negative mother will be Rh(D) positive simply as a result of the fathers genotype. Kernicterus can cause brain damage and presents with severe jaundice.
• ABO incompatability is common but haemolytic disease caused by it is rare. AB antigens are wekaly expressed in the foetus and newborn and as they are distributed more widely the antibodies are absorbed before they reach the foetal circulation.