Alloimmunisation to Blood Group

Antigens
“Diagnostic Approach”

Abdullah Meshi, BMSc (CLSc), MSc(UK).

Head of blood bank
King Fahd central Hospital-Jazan
aalmashi@hotmail.com
Introduction
 New advances in molecular biology have
revolutionised the way we look to both diagnosis
and management of human pathologies.

 One major role of MB in transfusion medicine is

the application of recombinant technology.

 A good example is to produce a recombinant

forms of RBC antigens for practical applications
Presentation Outlines
 Blood group systems & Immune response to
RBC antigens.

 Clinical significance of RBC alloantibodies.

 Current and future methods for Abs

identification
Blood Group Systems
Blood Group Systems
Blood Group Systems
Alloimmunisation to Red Cell
Antigens

What does immune

system do??
Immune Response to Blood Group Antigens

 Primary IR  Secondary IR
◦ Slow (weeks to ◦ Rapid
months ◦ Ab titer rising 48 hrs
◦ Low level of IgM ◦ IgG , peaks 6 days
◦ Needed high dose of after injection
Ag. ◦ Need smaller Ag dose
Immune Response to Blood Group Antigens

 T-cell-dependent antibody formation

Immune Response to Blood Group Antigens
Immune Response to Blood Group Antigens

 Sources of alloimmunisation to RBC antigens:

◦ Blood transfusion

◦ pregnancy
Immune Response to Blood Group Antigens

 Immunogenicity
◦ The ability of an antigen to stimulate an immune
response or antibody production.
◦ Most blood group antigens are poor immunogens
(<1% of transfused patients).

 Factors that affect immunogenicity:

◦ Foreignness, high molecular weight, chemical
complexity.
◦ Dose and route of administration.
◦ Genetic factors (HLA-DR genes).
Immune Response to Blood Group Antigens
Blood group antibodies detected in SCD patients at (KFCH), Jazan (n=362) *

Antibodies Detected Number of Patients

anti-K 10 (2.8%)
anti-E 9 (2.5%)
anti-c 6 (1.6%)
anti-Lea 5 (1.4%)
anti-M 4 (1.1%)
anti-E, c 3 (0.8%)
anti-Leb 2 (0.5%)
anti-S 1(0.3%)
anti-D & anti-C 1(0.3%)
anti-c, E & K 1(0.3%)
anti-Lea & Leb 1(0.3%)
anti-Xga 1(0.3%)
others 6 (1.6%)
Total * Abdullah S. & Meshi A., 2006 (unpublished data)
50 (13.8%)
Clinical significance of Red Cell alloantibodies

 Acute Haemolytic transfusion reaction (AHTR)

◦ Most blood group antibodies can cause AHTR

 Delayed haemolytic transfusion reaction

(DHTR)
◦ Most blood group antibodies can cause DHTR

 Haemolytic disease of the foetus and

newborn (HDFN)
◦ Rh & Kell antibodies.
Current Abs detection & Identification Methods

 Liquid-phase (tube/plate)

 Column-agglutination (gel cards)

 Solid-phase (microplate coated with RBCs)

Liquid-phase method

4+ 4+ 3+ 2+ 1+ 0
Column-agglutination (gel cards) method
Gel Card Method
Gel Card Method
Gel Card Method
Gel Card Method
Gel Card Method
Gel Card Method
Gel Card Method
Gel Card Method
Gel Card Method
Problems with current methods

 Rely on red blood cells

• Short half-life → problems of storage & distribution
• Difficult to find rare phenotype
• Concurrently Express many blood group antigens →
serological complexity
• Carry potential biohazard risks → infection
• Quality?? → main cause of errors in Ab
identification (NEQAS)
 Production of Recombinant Blood Group
Antigens

 The genes encoding most of the major blood

group determinants have been cloned &
sequenced
 Recombinant DNA technology was applied to
engineer clinically significant blood group
antigens (e.g. Kell, Duffy, Gerbich).
 These recombinant antigens can be used in

detecting & identifying Abs in clinical laboratories

Principle of blood group Antigen Engineering
Principle of blood group Antigen Engineering
Principle of blood group Antigen Engineering

Antigen capture ELISA*

0.14
0.12
Mean OD (minus

0.1
blank)

0.08 anti-K
0.06 anti-Kpa
0.04 anti-k

0.02
0
srFLAG-K/Kpa/Jsa K300
FLAG-Kell fusion protein

Meshi A., 2005 (unpublished data)

In Conclusion,,,,,
Suspension Bridge
Bristol, UK (2005)

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