HLA Antibodies Flashcards
HLA antibodies
- results from exposure to non-self HLA antigens (non-naturally occurring)
most common exposures to HLA antigens
- blood transfusion
- pregnancy
- previous transplant/ tissue
Clinical Relevance of HLA antibodies
- Important to detect so crossmatch results can be interpreted and even predicted
- Screening is performed on all potential transplant recipients and repeated while they are waiting for transplant
- Must be repeated following any potential immunizing event (ie. blood transfusion)
Epitopes vs Allo-epitopes
Epitope:
- A unique shape or marker carried on an antigen’s surface that triggers a corresponding antibody response
- Parts of an antigen molecule which contact the antigen-binding site of an antibody or T-cell receptor
Allo-epitope:
- Epitopes that differ among individual members of the same species
CREG
Cross Reactive Group Epitope:
- HLA antibodies that react with more than one gene
product/allele
- Believed to be a part of a shared or
cross-reactive “public epitope”
- Widely distributed among HLA molecules
Cross Reactivity
- Shared epitopes result in cross-reactivity between HLA antigens
- Cross-reactive antibodies are commonly seen in HLA
antibody analysis
= Can result in multiple antibodies from an exposure to one mis-matched antigen
Example of a Public Epitope
- Bw4: 73% in Canadian Population
- Bw6: 83% in Canadian Population
T or F: If a donor has HLA-A2 but the recipient does NOT, they will produce anti-A2 ONLY
FALSE; If a donor has HLA-A2 but the recipient does NOT, they will produce anti-A2 AND OTHER antibodies that have a shared epitope with A2
HLA XM
- XM involves incubation of donor cells with recipient serum
- Tests for pre-formed antibodies in recipient against donor
- Multiple sera samples may be used
- Two methods used locally (CDC-AHG & Flow Cytometry XM)
Interpretation of the HLA Crossmatch
The crossmatch should be interpreted after reviewing:
- Recipient HLA typing
- Recipient HLA antibody screenin
- Donor HLA typing
Transplant patients may have HLA antibodies from:
- Previous transplant (especially kidney recipients)
- Previous transfusions
- Pregnancy
NOTE: Many of the patients on our renal transplant wait list have antibodies to Class I, Class II, or both HLA antigens
Renal Patients listed for Deceased Donor Transplant
- Patients are listed by the Renal Transplant Service (RTS)
- HLA typed and have an HLA antibody screen before being added to list
- Once listed, patient sends monthly bloodwork to the HLA lab:
– for ongoing HLA antibody screening
– to have samples available for XM at all times
HLA Work Up of Deceased Kidney Donor
- Donor is HLA typed = entered into national donor registry
- A report is generated for the renal programs
—Donor HLA and matches to recipients on wait list
— Wait time
— HLA antibodies - Nephrologist decides selects recipients for donor
- If the recipients are high immunological risk, the HLA laboratory repeats the pre-transplant crossmatch with serum from that day
- The HLA lab freezes donor lymphocytes (from spleen/ lymph node) for future XM (in case of rejection)
What happens after the transplant ?
- Recipient is monitored by the transplant programs
- Post-transplant HLA antibody testing routinely done (look for antibodies against donor mismatched antigens)
- HLA antibody testing also done if patient’s allograft function is poor or deteriorates
- Other investigations (ie. biopsy)
- The recipient may be re-listed for transplant if the donated organ ceases to function
Why else may patient HLA be re-tested ?
- capture newly discovered antigens
- updated testing methods
- facilitate research studies
