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3. Transfusion > IBTS - HLA > Flashcards

IBTS - HLA Flashcards

1
Q

What is HLA

A

Human Leucocyte Antigen

Cell surface glycoproteins involved in antigen presentation to T cells

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2
Q

What is MHC

A

Major Histocompatibility Complex

The region of chromosome 6 which includes the genes coding for HLA proteins

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3
Q

What is the role of HLA antigens in the immune system

A

HLA type allows the immune system to discriminate from self and from non-self

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4
Q

What does class I MHC do?

A

Binds peptides derived from endogenously synthesised proteins (eg viral proteins in virus infected cells) they present the peptides to CD8+ T cells (primarily cytotoxic T cells)

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5
Q

What does class II MHC do?

A

Bind proteins from exogenous proteins (ie those in the external medium) they are internalised by professional antigen presenting cells and presented to CD4+ T cells (primarily helper T cells).

This ensures that cells harbouring infectious agents are recognised and attacked by Class I restricted CTLs, whereas Class II restricted helper T cells respond to soluble antigens and activate antibody producing B cells.

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6
Q

Talk about the inheritance of HLA

A

Each person inherits two copies of chromosome 6 - one from mom and one from dad

HLA genes are very polymorphic -> thousands of different HLA alleles

HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, HLA-DP genes involved

e.g. over 2000 HLA-A alleles

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7
Q

What HLA labs do we have in the IBTS

A

A Molecular Biology lab
- HLA and HPA genotyping
- SOO, SSP, Gel electrophoresis, NGS etc

Serology lab
- screening patient sera for anti-HLA and anti-HPA alloantibodies

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8
Q

Why would we need to carry out HLA typing
(6)

A

Haematopoietic stem cell transplant -> HLA matching

Platelet refractoriness -> HPA antibodies

TRALI -> HLA antibodies

Disease susceptibility e.g. ankylosing spondylitis

Drug sensitivity e.g. abacivar

Forensic investigations

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9
Q

Write about HLA and ankylosing spondylitis

A

Disease causing fusion of the vertebrae

HLA-B*27

90% of people with AS have the HLA*27 gene

Doesn’t mean you will have the disease but high association

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10
Q

Write about Abacivar and HLA

A

Abacivar is a reverse transcriptase inhibitor used in the treatment of HIV/AIDS

A single nucleotide polymorphism at HLA B*57:01 has been associated with hypersensitivity to this drug

Very rare but hypersensitivty can be fatal so patients are typed before administering the drug

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11
Q

Give three sources of cells for allogenic transplants

A

Bone marrow
Peripheral stem cells
Cord blood

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12
Q

Give four different types of donors used in transplants

A

HLA identical siblings - preferred
Unrelated but matched donor
Sibling/unrelated mm
Haploidentical

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13
Q

Why are HLA antigens so important in transplants

A

HLA antigens are the major antigens which determine the compatibility of transplanted tissues and organs

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14
Q

What occurs in HLA unmatched transplants

A

Graft versus host disease

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15
Q

When might you want GvHD

A

Want a degree of it when a bone marrow transplant is given to leukaemia patients

Want graft versus leukaemia affect

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16
Q

What is Graft vs Host disease

A

This is where the donor white blood cells recognise the host tissue as foreign and initiate an immune response

Acute or chronic

Unrelated donor transplants are associated with an increased incidence of acute GvHD and graft failure compared to matched donors

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17
Q

Talk about acute GvHD

A

Occurs in less than 100 days post transplant

Affects the skin, liver and GIT

Occurs in 40% of sibling transplant and 50% of unrelated donors

18
Q

Talk about chronic GvHD

A

> 100 days post transfusion

Affects skin, liver, gut (as in acute) but also affects eyes, glands, CT and lungs

19
Q

What is IUBMR

A

Irish Unrelated Bone Marrow Registry

20
Q

What is the Irish Unrelated Bone Marrow Registry

A

A registry of donors who are prepared to donate to a matched patient

The IUBMR performs unrelated searches on behalf of the adult and paediatric services

Not ideal -> ideal donor is a HLA matched sibling -> 1 in 4 chance of a sibling being a match

Smaller family sizes means IUBMR being used more now

21
Q

What is the gold standard resolution method for HLA typing

A

Next generation sequencing

Serology can be used but its very low resolution in comparison to NGS

22
Q

What HLA typing methods can be used

A

SSO for HLA typing
SSP for HLA typing
Luminex for HLA antibody screening and ID
Sanger sequencing for high resolution HLA typing
NGS for high resolution HLA typing

23
Q

How is DNA extraction carried out for HLA typing

A

Ez1 Biorobot

Magentic particle technology

Pre-filled, sealed reagent cartridges

Pre-programmed cards with different protocols

Complete automation of nucleic acid purification with no manual centrifugation steps

24
Q

What is SSO

A

Sequence Specific Oligonucleotide

Also called Histo Spot

Histo Spot assay with Mr spot processor allows automated SSO typing

Low to medium resolution

Can type up to 96 samples at a time

25
Q

What is SSP

A

Sequence Specific Primers

Works by targeting a particular DNA sequence

Several PCRs are preformed with a battery of SSPs which will amplify only alleles with sequences complementary to the primers

The presence of amplified material indicates the presence of the corresponding allele or group of alleles

The PCR product is seen as band on a gel

Advantages: particularly used for high resolution typing and is relatively fast

Disadvantages: laborious, small sample numbers

26
Q

Talk about Sanger sequencing

A

Capillary based Sanger sequencing

Class I (A, B, C) Exons 2, 3 and 4

Class II (DRB1, DQB1) Exons 2 and 3

Group specific sequencing primers used to resolve ambiguities

Software processes the DNA sequence data and assigns a HLA type by camparison with a database

27
Q

Why are anti-HLA antibodies important

A

Platelet refractoriness

Donor specific antibodies

28
Q

Why are anti-HPA antibodies important

A

Platelet refractoriness (where HLA has been ruled out)
Neonatal alloimmune thrombocytopenia (NAIT)
Post transfusion purpura (PTP)

29
Q

Define platelet refractoriness

A

The failure, in two consecutive transfusions of ABO identical platelets <3 days old, to achieve a corrected count increment (CCI) of 7.5 ay 15 minutes to 1 hour after the platelet transfusion

i.e. the platelet transfusion does nothing

30
Q

What are the two types of platelet refractoriness

A

Non-immune mediated
Immune mediated

31
Q

What is the corrected count increment for platelets

A

7.5 after 15 mins to 1 hour

32
Q

What are the two types of platelet refractoriness

A

Non-immune mediated
- fever
- infection
- hypersplenism
- bleeding

Immune mediated
- antibodies!

33
Q

What are the two main causes of immune platelet refractoriness

A

Anti-HLA
Anti- HPA

34
Q

How do we screen for platelet refractoriness antibodies

A

Luminex technology
- flow cytometry based instrument
-

35
Q

What are donor specific antibodies

A

Made when a stem cell transplant patient receives a HLA mismatched transplant

Could cause graft rejection

Can reduce antibody titre through plasmapheresis or may need to look at alternative donors

36
Q

What are anti-HPA antibodies

A

Antibodies produced against antigens on platelets

Human platelet antigens are polymorphisms in platelet membrane glycoproteins that can stimulate production of alloantibodies once exposed to foreign platelets with different HPAs

37
Q

What complications are caused by anti-HPA antibodies

A

Platelet refractoriness
- no response to platelets
- usually the cause when HLA antibodies ruled out

Neonatal alloimmune thrombocytopenia (NAIT)

Post transfusion purpura (PTP)

38
Q

What is NAIT

A

Neonatal Alloimmune Thrombocytopenia

Severe thrombocytopenia caused by maternal alloimmunisation against human platelet antigens present on fetal cells (platelet version of HDFN)

39
Q

What is the most common type of NAIT

A

HPA-1a -> seen in 80% of cases
HPA-5b seen in 5-15% of cases

40
Q
A
41
Q
A

3. Transfusion (14 decks)

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