HLA sensitization and crossmatch testing

The purpose of HC tests is to recognize the immunologic risk of a TR in the context of a possible donor. If Tx occurs between genetically different in

 

HLA sensitization and crossmatch testing

 

Abbreviations:

o   HC: histocompatibility.

o   MHC: major histocompatibility complex.

o   HLAs: the human leukocyte antigens.

o   DSA: donor-specific anti-HLA antibody.

o   CDC: complement-dependent cytotoxic.

o   KTx: kidney transplantation.

o   SAB: single-antigen bead.

o   AB: antibodies.

o   Ag: antigen

o   CX: crossmatch.

o   Bld Tx: blood transfusions.

o   im/m: Immunosuppression.

o   TR: transplant recipient.

o   SOT: solid organ Tx.

o   KTx: kidney transplant.

o   cPRA: The calculated panel of reactive antibody.

o   Snz: sensitization

o   DCD: deceased-donor.

o   Chr: Chromosome.

o   FCM: flow cross matches

 

The purpose of HC tests is to recognize the immunologic risk of a TR in the context of a possible donor. If Tx occurs between genetically different individuals, the allogeneic graft (allograft) is identified as a foreign primarily owing to the difference between donor/TR MHC molecules that are known also as the HLAs. The developed immune response observed via 2 main mechanisms: T cell-mediated (cellular) response & AB-mediated (humoral) response. The current HC tests are focusing primarily on anticipating the AB-mediated alloimmune response.

 

In human being, the MHC genes are involved on the short arm of Chr 6 & include the class I, HLA-A, HLA-B, & HLA-C, and class II genes, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, & HLA-DRB5. Class I molecules are being expressed on any nucleated cell, whilst class II molecules are being expressed mainly on Ag-presenting cells (e.g., B cell, dendritic cell, & macrophage) but can be also expressed with inflammatory states on variable cell types that includes endothelial cell & epithelial cell.  

 

In SOT, a "mismatching" refers to an HLA Ag(s) present on the cells of the donor’s allograft but not present in the TR. The higher the disparity between the donor & TR, the greater "foreign" the allograft appearance and the increased likelihood of the evolution of an allo-immune responses. In the subset of DCD KTx allocation, only the HLA-A, HLA-B, & HLA-DR loci are tested for mismatching. Accuracy in typing of a donor's & recipient's HLAs is crucial in recognizing the magnitude of mismatching between them and in discarding the tx of potential donors’ organs that express HLA Ag against which the TR has developed AB(s).

In certain ptns it is better to discard exposing a potential candidate to certain organ bearing mismatched HLA Ag against which the potential candidate with prior formation of AB. HLA typing was previously proceeded via serology-based assessment, but this has been substituted by the application of the DNA-based molecular technique that provides a better resolution and more accuracy in the typing of all loci.  

 

Almost 30 % of ptns on the waiting list are proved to have AB(s) directed against one or more HLAs, owing to prior sensitization due to previous exposures, e.g.,:

1)    Bld Tx,

2)    Prior Tx,

3)    Pregnancy, &

Implants e.g., [ventricular assisting device & homograft]. The purpose of screening ptns for anti-HLA AB before Tx:

1)    Recognizing the presence of anti-HLA AB (s),

2)    Estimating their specificity to certain HLA Ag (s), &

3)    Determining their relative amounts and their potential strength.

These basal data will assist the physician in assessment:

1)    The likelihood to receive an HLA-compatible Tx,

2)    Recognizing the "unaccepted Ags" & avoiding grafts with these Ag(s), &

3)    Identifying ptns with higher immunologic risk and providing more aggressive im/m. plan and/or more strict post-tx surveillance.  

 

The cPRA is a method enabling the clinician assessing a ptn's magnitude of Snz to HLA Ag(s) and consequently the likelihood for Tx. The cPRA can calculate the likelihood of tx via interpreting the results of the SAB assay to recognize the specificity of the anti-HLA AB, combined with the known frequency of HLA Ag(s) within the donor cohorts.

 

The purpose of CX assay is to recognize any prior DSA found in a ptn's serum and directed against a specific donor.

Cell-based assay e.g., CDC CX & FCM are usually proceeded tx to decide whether ptn is amenable to proceed in tx. Results of ALL HLA tests should be incorporated to assess the potential immunologic risk between a donor & TR pair. Moreover, the decision to postpone or proceed with Tx should also take into consideration the associated clinical criteria e.g.,

1)    Donor issues.

2)    Tx organ type,

3)    How urgent is Tx,

4)    Type of im/m. regimen for a potential TR, &

5)    Availability of receiving a compatible graft.