Faculty of Allied Medical Science Blood Banking (MLBB 201)

CLINICAL SIGNIFICANCE OF RC ANTIBODIES Prof. Dr. Nadia Aly Sadek Director of Blood Bank Centre Prof. in Haematology MRI- University of Alexandria

Outcomes By the end of this lecture, the students will be able to: Clinical significance of rc antibodies. Clinical significance of rc antibodies. Factors affecting the clinical significance of antibodies. Factors affecting the clinical significance of antibodies.

RC antibodies may be: - Naturally occurring: not ellicited by any stimulus - Immune-induced: ellicited by blood transfusion pregnancy, malignancy.

Thay are classified into: - Alloantibodies: in response to an antigen lacking on the individual RCs. - Auto antibodies having specificity against an antigen present on the individual ’ s own RCs.

They are responsible for :- 1- Haemolytic Transfusion Reaction (HTR): the antibody destroys antigen-positive transfused RCs. They are directed to ABO system, they are IgM in nature hence, they can activate the complement cascade causing intravascular hemolysis.

2- Haemolytic disease of the fetus and newborn (HDFN) IgG maternally derived antibody is directed against a paternally derived- antigen on the fetal or neonatal red cells, crosses the placenta and destroys the fetal RCs. IgG maternally derived antibody is directed against a paternally derived- antigen on the fetal or neonatal red cells, crosses the placenta and destroys the fetal RCs.

3- Hemolytic anaemia (HA) An autoantibody against “ self “ antigens is produced and causes increased red cell destruction. These antibodies may be warm reactive or react optimally in the cold. An autoantibody against “ self “ antigens is produced and causes increased red cell destruction. These antibodies may be warm reactive or react optimally in the cold.

Factors affecting the clinical significance of AbS All antibodies bind to the appropriate antigen. They are clinically significant when they have the potential to initiate accelerated destruction of RCs carrying the cognate antigen whether it is immune, naturally occurring or auto antibody.

Several factors play a role: 1- Antibody specificity 2- Concentration and avidity 3- Thermal amplitude: below 30 degrees, it is not important. 4- IgG class/subclass (IgG1, IgG3)

5- Activity of of the mononuclear phagocytic system 6- Antigen site density and mobility of the antigen in the membrane. 7- Volume of RCs administered 8- Soluble blood group substances may neutralize the Ab (Lewis substance).

Mechanisms of RC destruction 1- By Ab-dependent cytotoxic mechanism 2- Lysosomal enzymes released by mononuclear cells effect the destruction, however, both phagocytosis and cytotoxicity may occur at the same time.

Antigen loss This occurs when the Ab induces the loss of its target Ag without significant damage to the cells themselves. This is also known as “ depressed Ag ”, “ Ag suppression ” and “ antigenic modulation ”. This phenomenon has been observed for multiple blood groups as well as Ags on leukocytes, platelets and neoplastic cells.

Antigen loss is most often observed in the Kell system, the Rh system may be also involved. The DAT may be negative for few days and then becomes weakly positive. Viral infection may decrease Kell synthesis during erythropoiesis. The spleen may participate in Ag loss.

Acquired changes in blood groups 1- Group A individuals may acquire a B Ag and become AB. The B Ag is generally weak and the A Ag is weakened. This occurs in patients with GIT diseases, especially cancer colon. Bacterial enzymes in the blood remove the acetyl group from D-acetyl galactosamine

(Group A Ag) to produce alpha galactose (similar to blood group B Ag). 2- Weakening of A Ag is common in group A patients with acute myeloid leukaemia (AML). Sometimes 2 populations of cells are present (A and … )

3- Modifications of ABH antigens are manifest before the diagnosis of malignancy and therefore indicate a pre- leukaemic state. 4- A or B Ags on RBCs can be abolished in vitro by converting them back to H Ag by enzymes such as chryseobacrterium

(A-zyme) or green coffeee beans (B-zyme). This is the basis of the universal blood group

Blood groups and diseases - Group A individuals are more susceptible to cancer stomach and colon. They have hypoacidity, normally and need orange juice and Vit B12 regularly. - Group O individuals are more susceptible to gastric and duodenal ulcers (hyperacidity).

Study question Write a short note about the Mechanisms of RC destruction.

Assignments Changes that occur in a blood bag Changes that occur in a blood bag ايمن السعيد ايمن السعيد

Thank You