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

Antigen presenting cell

HLA

peptide

T cell

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

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

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

HLA antibody mediated HLA antibody mediated immune reactionsimmune reactions

Leukocyte Pyrogenic cytokines

FNHTR

Platelets Immunological platelet refractoriness

Graft

Hyperacute/acute graft rejection

HLA antibodiesHLA antibodies

Induced by • Pregnancy• Transfusion • Transplantation

Prevention of allo-Prevention of allo-sensitisationsensitisation

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

UVB irradiation

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?

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