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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.

Jan 02, 2016

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Page 1: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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

Page 2: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

The Human Leukocyte Antigen The Human Leukocyte Antigen (HLA) System(HLA) System

• Highly polymorphic cell surface molecules

• First identified and characterised in leukocytes

Page 3: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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

Page 4: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

Function of HLA molecules –Function of HLA molecules –IImmune recognitionmmune recognition

Antigen presenting cell

HLA

peptide

T cell

Page 5: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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

Page 6: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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

Page 7: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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

Page 8: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

HLA antibody mediated HLA antibody mediated immune reactionsimmune reactions

Leukocyte Pyrogenic cytokines

FNHTR

Platelets Immunological platelet refractoriness

Graft

Hyperacute/acute graft rejection

Page 9: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

HLA antibodiesHLA antibodies

Induced by • Pregnancy• Transfusion • Transplantation

Page 10: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

Prevention of allo-Prevention of allo-sensitisationsensitisation

Leuko-reduction• Prevents direct allo-recognition• Inhibits indirect allo-recognition• Removes antibody target in FNHTR

UVB irradiation

Page 11: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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?

Page 12: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

Donor selection Donor selection 1. Unmatched

compatible donor• Crossmatch• Antigen negative

approach – single antigen assay

• HLA matchmaker

2. Matched donor

Page 13: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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

Page 14: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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)

Page 15: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

TRALITRALI

Endothelial cell

neutrophile

Anti HLA/HNA antibody Chemotactic factors

Adherence to pulmonary endothelium/epithelium

Pulmonary edema

Page 16: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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)

Page 17: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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

Page 18: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

Prevention of graft versus Prevention of graft versus host diseasehost disease

• Choosing HLA matched donors

• Irradiation – Inactivates viable lymphocytes

Page 19: The Ubiquitous HLA System: applications in transfusion and transplantation Dr Mary Purna Chacko Department of Transfusion Medicine and Immunohaematology.

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