The Ubiquitous The Ubiquitous HLA System: HLA System: applications in applications in transfusion and transfusion and transplantation transplantation Dr Mary Purna Chacko Dr Mary Purna Chacko Department of Transfusion Medicine and Department of Transfusion Medicine and Immunohaematology Immunohaematology Christian Medical College and Hospital, Christian Medical College and Hospital, Vellore Vellore ISBTI 2012 ISBTI 2012
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The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.
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The Ubiquitous The Ubiquitous HLA System: HLA System:
applications in applications in transfusion and transfusion and transplantationtransplantation
Dr Mary Purna ChackoDr Mary Purna ChackoDepartment of Transfusion Medicine and Department of Transfusion Medicine and
ImmunohaematologyImmunohaematologyChristian Medical College and Hospital, Christian Medical College and Hospital,
VelloreVelloreISBTI 2012ISBTI 2012
The Human Leukocyte Antigen The Human Leukocyte Antigen (HLA) System(HLA) System
• Highly polymorphic cell surface molecules
• First identified and characterised in leukocytes
HLA expressionHLA expression
• Class I (HLA A, B and C)– all nucleated cells and platelets
• Class II (HLA DR, DQ and DP)– B cells, activated T cells, macrophages, dendritic cells
Function of HLA molecules –Function of HLA molecules –IImmune recognitionmmune recognition
To what percentage of the population does the patient have antibodies?
What is his chance of getting a
compatible donor?
What are the antigens against which the patient has antibodies? Which donors
should be avoided?
Does the patient
have anti-HLA
antibodies?
Donor selection Donor selection 1. Unmatched
compatible donor• Crossmatch• Antigen negative
approach – single antigen assay
• HLA matchmaker
2. Matched donor
HLA inheritance HLA inheritance Father Mother
Child 1 Child 2 Child 3 Child 4
Chance of having an HLA identical sibling =1-(0.75)n
Haplotype A
Haplotype B
Haplotype C
Haplotype D
Haplotype A Haplotype A
Haplotype C Haplotype D
Haplotype B
Haplotype C
Haplotype B
Haplotype D
HLA related immune reactionsHLA related immune reactions
OF DONOR AGAINST RECIPIENT• Transfusion associated acute lung injury (TRALI)• Transfusion associated graft versus host disease
(TA GVHD)
TRALITRALI
Endothelial cell
neutrophile
Anti HLA/HNA antibody Chemotactic factors
Adherence to pulmonary endothelium/epithelium
Pulmonary edema
PREVENTION OF TRALIPREVENTION OF TRALI
• Antibodies most commonly found in multiparous women
• Avoid use of female donor plasma**Eder et al (Transfusion 2010); Nakazawa et al (Transfusion 2009)
Graft versus Host DiseaseGraft versus Host Disease
1. Transfer of viable lymphocytes
2. Inability of host to mount immune response
3. Sharing of HLA haplotypes prevents recipient from recognising donor tissue as foreign
A2 B7
A2 B7
A2 B7
A3 B35
Prevention of graft versus Prevention of graft versus host diseasehost disease
• Choosing HLA matched donors
• Irradiation – Inactivates viable lymphocytes
If we cannot end our differences, at If we cannot end our differences, at least we can make the world safe for least we can make the world safe for diversitydiversityJohn F. KennedyJohn F. Kennedy