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
- HLA antibodies are important to detect and define so that crossmatch results can be interpreted and even predicted
- Antibody 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 in response to a shared or
cross-reactive epitope “public epitope”
- Many of the public epitopes are 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 - As a result, patients can make 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 (or
sera) - Test determines if there is pre-formed antibody in recipient to
donor - Multiple sera samples may be used
- Two methods for crossmatch are
used locally (CDC-AHG & Flow Cytometry XM)
Interpretation of the HLA Crossmatch
The crossmatch should be interpreted with review of:
- Recipient HLA typing
- Donor HLA typing
- Recipient HLA antibody screening results
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 for renal transplant by
the Renal Transplant Service (RTS) - They are HLA typed and have an HLA antibody screen prior to being added to the transplant list
- Once listed/activated on the transplant list, each patient sends monthly bloodwork to the HLA laboratory for ongoing HLA antibody screening and to have samples available for XM at all times
HLA Work Up of Deceased Donor
- The donor is HLA typed
- The HLA typing is entered into our national donor registry (to search for good matches in the highly sensitized kidney patient
waitlist) - A report is generated for the renal programs
—Donor HLA and matching to recipients on wait list
— Wait time
— HLA antibodies - The nephrologist on call decides which recipients to select for the donor
- If the recipients are high immunological risk, the HLA laboratory repeats the pre-transplant crossmatch with serum from that day
- The HLA laboratory freezes donor lymphocytes for future XM in case of rejection
- Cells are extracted from donor spleen or lymph node
Outcome of Transplant
- The recipients’ transplant outcomes are monitored by the transplant programs
- Post-transplant HLA antibody testing is routinely done to look for antibodies to the donor mismatched antigens
- HLA antibody testing is also done if the patient’s allograft function is poor or deteriorates
- Other investigations such as biopsy would also be done
- The recipient may be re-listed for transplant if the donated organ ceases to function
Why may patient HLA be re-tested ?
- capture newly discovered antigens
- updated testing methods
- facilitate research studies
