Faculty of Allied Medical Faculty of Allied Medical ScienceScience

Blood Banking (MLBB 201)Blood Banking (MLBB 201)

CLINICAL CLINICAL SIGNIFICANCE OF RC SIGNIFICANCE OF RC

ANTIBODIESANTIBODIESProf. Dr. Nadia Aly SadekProf. Dr. Nadia Aly Sadek

Director of Blood Bank CentreDirector of Blood Bank CentreProf. in HaematologyProf. in Haematology

MRI- University of AlexandriaMRI- University of Alexandria

OutcomesOutcomes

By the end of this lecture, the students By the end of this lecture, the students will be able to:will be able to:

Clinical significance of rc antibodies.Clinical significance of rc antibodies. Factors affecting the clinical Factors affecting the clinical

significance of antibodies.significance of antibodies.

RC antibodies may be:RC antibodies may be:

- Naturally occurring: not ellicited by - Naturally occurring: not ellicited by any stimulusany stimulus

- Immune-induced: ellicited by blood - Immune-induced: ellicited by blood transfusion pregnancy, malignancy.transfusion pregnancy, malignancy.

Thay are classified into:Thay are classified into:

- Alloantibodies: in response to an - Alloantibodies: in response to an antigen lacking on the individual RCs.antigen lacking on the individual RCs.

- Auto antibodies having specificity - Auto antibodies having specificity against an antigen present on the against an antigen present on the individualindividual’’s own RCs.s own RCs.

They are responsible for :-They are responsible for :-

1- 1- Haemolytic Transfusion Reaction Haemolytic Transfusion Reaction (HTR): the antibody destroys antigen-(HTR): the antibody destroys antigen-positive transfused RCs.positive transfused RCs.

They are directed to ABO system, they They are directed to ABO system, they are IgM in nature hence, they can are IgM in nature hence, they can activate the complement cascade activate the complement cascade causing intravascular hemolysis.causing intravascular hemolysis.

22 - -Haemolytic disease of the Haemolytic disease of the fetus and newborn (HDFN)fetus and newborn (HDFN)

IgG maternally derived antibody is IgG maternally derived antibody is directed against a paternally derived- directed against a paternally derived- antigen on the fetal or neonatal red antigen on the fetal or neonatal red cells, crosses the placenta and cells, crosses the placenta and destroys the fetal RCs.destroys the fetal RCs.

33 - -Hemolytic anaemia (HA)Hemolytic anaemia (HA)

An autoantibody against An autoantibody against ““ self self ““ antigens is produced and causes antigens is produced and causes increased red cell destruction. These increased red cell destruction. These antibodies may be warm reactive or antibodies may be warm reactive or react optimally in the cold.react optimally in the cold.

Factors affecting the clinical Factors affecting the clinical significance of AbSsignificance of AbS

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

Several factors play a roleSeveral factors play a role::

11 - -Antibody specificityAntibody specificity

22 - -Concentration and avidityConcentration and avidity

33 - -Thermal amplitude: below 30 Thermal amplitude: below 30 degrees, it is not importantdegrees, it is not important..

44 - -IgG class/subclass (IgG1, IgG3)IgG class/subclass (IgG1, IgG3)

55 - -Activity of of the mononuclear Activity of of the mononuclear phagocytic systemphagocytic system

66 - -Antigen site density and mobility of Antigen site density and mobility of the antigen in the membranethe antigen in the membrane..

77 - -Volume of RCs administeredVolume of RCs administered

88 - -Soluble blood group substances may Soluble blood group substances may neutralize the Ab (Lewis substance)neutralize the Ab (Lewis substance)..

Mechanisms of RC Mechanisms of RC destructiondestruction

11 - -By Ab-dependent cytotoxic By Ab-dependent cytotoxic mechanismmechanism

22 - -Lysosomal enzymes released by Lysosomal enzymes released by mononuclear cells effect the mononuclear cells effect the destruction, however, both destruction, however, both phagocytosis and cytotoxicity may phagocytosis and cytotoxicity may occur at the same timeoccur at the same time..

Antigen lossAntigen loss

This occurs when the Ab induces the loss of This occurs when the Ab induces the loss of its target Ag without significant damage its target Ag without significant damage to the cells themselvesto the cells themselves..

This is also known as This is also known as ““depressed Agdepressed Ag””, , ““Ag Ag suppressionsuppression”” and and ““ antigenic modulation antigenic modulation””..

This phenomenon has been observed for This phenomenon has been observed for multiple blood groups as well as Ags on multiple blood groups as well as Ags on leukocytes, platelets and neoplastic cellsleukocytes, platelets and neoplastic cells..

Antigen loss is most often observed in Antigen loss is most often observed in the Kell system, the Rh system may the Kell system, the Rh system may be also involved. The DAT may be be also involved. The DAT may be negative for few days and then negative for few days and then becomes weakly positivebecomes weakly positive..

Viral infection may decrease Kell Viral infection may decrease Kell synthesis during erythropoiesissynthesis during erythropoiesis..

The spleen may participate in Ag lossThe spleen may participate in Ag loss . .

Acquired changes in blood Acquired changes in blood groupsgroups

11 - -Group A individuals may acquire a B Group A individuals may acquire a B Ag and become AB. The B Ag is Ag and become AB. The B Ag is generally weak and the A Ag is generally weak and the A Ag is weakenedweakened..

This occurs in patients with GIT This occurs in patients with GIT diseases, especially cancer colondiseases, especially cancer colon..

Bacterial enzymes in the blood remove Bacterial enzymes in the blood remove the acetyl group from D-acetyl the acetyl group from D-acetyl galactosaminegalactosamine

((Group A AgGroup A Ag ) )to produce alpha galactose to produce alpha galactose )similar to blood group B Ag()similar to blood group B Ag(..

22 - -Weakening of A Ag is common in Weakening of A Ag is common in group A patients with acute myeloid group A patients with acute myeloid leukaemia (AML). Sometimes 2 leukaemia (AML). Sometimes 2 populations of cells are present (A populations of cells are present (A and and ……))

33 - -Modifications of ABH antigens are Modifications of ABH antigens are manifest before the diagnosis of manifest before the diagnosis of malignancy and therefore indicate a malignancy and therefore indicate a pre-leukaemic statepre-leukaemic state..

44 - -A or B Ags on RBCs can be abolished A or B Ags on RBCs can be abolished in vitro by converting them back to H in vitro by converting them back to H Ag by enzymes such as Ag by enzymes such as chryseobacrteriumchryseobacrterium

((A-zymeA-zyme ) )or green coffeee beans )B-zyme(or green coffeee beans )B-zyme(..

This is the basis of the universal blood This is the basis of the universal blood groupgroup

Blood groups and diseasesBlood groups and diseases

- -Group A individuals are more Group A individuals are more susceptible to cancer stomach and susceptible to cancer stomach and colon. They have hypoacidity, colon. They have hypoacidity, normally and need orange juice and normally and need orange juice and Vit B12 regularlyVit B12 regularly..

- -Group O individuals are more Group O individuals are more susceptible to gastric and duodenal susceptible to gastric and duodenal ulcers (hyperacidity)ulcers (hyperacidity) . .

Study questionStudy question

Write a short note about the Write a short note about the Mechanisms of RC destructionMechanisms of RC destruction..

AssignmentsAssignments

Changes that occur in a blood bagChanges that occur in a blood bag

السعيد السعيد ايمن ايمن

Thank YouThank You