The Ubiquitous HLA System: applications in transfusion and transplantation
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Transcript of The Ubiquitous HLA System: applications in transfusion and transplantation
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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
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The Human Leukocyte Antigen The Human Leukocyte Antigen (HLA) System(HLA) System
• Highly polymorphic cell surface molecules
• First identified and characterised in leukocytes
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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
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Function of HLA molecules –Function of HLA molecules –IImmune recognitionmmune recognition
Antigen presenting cell
HLA
peptide
T cell
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Allo-recognitionAllo-recognition
Donor antigen
presenting
cell
Recipient T cell Recipient T cell
Recipient antigen presenting cell
TCR TCR
donor HLA
peptide
Recipient HLA
donor HLA peptide
Processing and presentation by recipient APC
DIRECT INDIRECT
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HLA typingHLA typing
• Serology eg. HLA B7• Molecular
– low resolution – PCR SSP, PCR SSOP eg. HLA B*07
– Subtype – High resolution PCR SSP, PCR SSOP, SBT eg.HLA B*07:01
– Non coding polymorphisms - SBT eg.HLA B*07:01:01
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HLA related immune reactions HLA related immune reactions OF RECIPIENT AGAINST DONOR TISSUE
HUMORAL IMMUNITY
• Febrile non-haemolytic transfusion reaction (FNHTR)
• Immunological platelet refractoriness (IPR)
• Humoral graft rejection
CELLULAR IMMUNITY
• Cellular graft rejection
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HLA antibody mediated HLA antibody mediated immune reactionsimmune reactions
Leukocyte Pyrogenic cytokines
FNHTR
Platelets Immunological platelet refractoriness
Graft
Hyperacute/acute graft rejection
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HLA antibodiesHLA antibodies
Induced by • Pregnancy• Transfusion • Transplantation
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Prevention of allo-Prevention of allo-sensitisationsensitisation
Leuko-reduction• Prevents direct allo-recognition• Inhibits indirect allo-recognition• Removes antibody target in FNHTR
UVB irradiation
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The allosensitised patient -The allosensitised patient -defining allosensitisationdefining allosensitisation
• Crossmatch • Mixed antigen screening assay• Percentage Panel Reactive Antibody
(PRA)assay• Single antigen assay
Does the patient have antibodies against this
donor?
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?
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Donor selection Donor selection 1. Unmatched
compatible donor• Crossmatch• Antigen negative
approach – single antigen assay
• HLA matchmaker
2. Matched donor
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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
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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)
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TRALITRALI
Endothelial cell
neutrophile
Anti HLA/HNA antibody Chemotactic factors
Adherence to pulmonary endothelium/epithelium
Pulmonary edema
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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)
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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
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Prevention of graft versus Prevention of graft versus host diseasehost disease
• Choosing HLA matched donors
• Irradiation – Inactivates viable lymphocytes
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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