Histocompatibility Testing: A Fundamental Aspect of Renal Transplant Workup
Abstract
:1. Introduction
2. Human Leukocyte Antigen (HLA) Typing
3. Anti-HLA Antibodies
4. Complement-Dependent Cytotoxicity Crossmatch (CDCXM)
5. Flow Cytometry Crossmatch (FCXM)
6. Panel-Reactive Antibodies (PRA)
7. Virtual Crossmatch (VXM)
Assay | HLA Source | Analysis | Interpretation |
---|---|---|---|
Anti HLA antibody (screening) | Most common Antigens (mixed and random) | Positive or negative | Does the patient possess any antibodies? |
Panel Reactive Antibodies (PRA) | Each bead is a phenotype of an individual | Positive (%) or negative | Extent of sensitization? |
Single-antigen bead (SAB) | One HLA antigen per bead | Positive or negative (Semi-Quantitative, MFI) | Does patient possess any DSA? |
Characteristic | Cell-Based Crossmatch (CDCXM and FCXM) | Virtual Crossmatch |
---|---|---|
Goal | Determine compatibility between prospective donor and recipient by testing for the presence of preformed antibodies. | Assess the percentage of the population to which a patient may be sensitized, indicating the likelihood of finding a compatible donor. |
Methodology | Involves mixing recipient’s serum with donor lymphocytes (T and B cells) cells to detect any preformed antibodies against donor antigens. | Utilizes HLA typing data to predict potential antibody reactions without physical mixing of donor’s cells. |
Interpretation | Provides information on the presence of preformed antibodies in the recipient. | Utilizes information about the recipient’s sensitization and the donor’s HLA antigens to predict the likelihood of a positive crossmatch. |
Assessment of Risk | Identifies immediate risk of rejection due to preformed antibodies. | Predicts the risk of a positive crossmatch based on the recipient’s antibody profile and the donor’s HLA antigen profile. |
CDC Crossmatch | Flow Crossmatch | Single-Antigen Bead (SAB) (Virtual Cross Match) | Perspective |
---|---|---|---|
Positive | Positive | Positive |
|
Negative | Positive | Positive |
|
Negative | Negative | Positive |
|
Positive | Positive | Negative |
|
Positive | Negative | Negative |
|
Negative | Positive | Negative |
|
8. Epitope-Based Matching Algorithms
9. Conclusions
10. Future Directions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | SSP HLA Typing | SSO HLA Typing | NGS HLA Typing |
---|---|---|---|
Methodology | PCR based, identifies specific DNA sequences using primers designed for known alleles. | Hybridization based, uses specific probes for known alleles. | High throughput DNA sequencing technology, reads entire HLA gene region. |
Resolution | Low to intermediate. | Low to intermediate. | High. |
Throughput | Low to moderate throughput, suitable for small-scale typing. | Moderate throughput, suitable for mid-scale typing. | High throughput, capable of processing a large number of samples simultaneously. |
Accuracy | Good accuracy for the targeted alleles. | Good accuracy for the targeted alleles. | High accuracy due to sequencing the entire gene region. |
Flexibility | Limited flexibility for detecting novel or unknown HLA alleles. | Limited flexibility for detecting novel or unknown HLA alleles. | Greater flexibility in detecting novel or unknown HLA alleles. |
Characteristic | CDCXM | FCXM |
---|---|---|
Methodology | Uses complement proteins to detect antibody binding and cell lysis. | Utilizes flow cytometry to assess the binding of antibodies to donor cells. |
Sensitivity | Generally less sensitive compared to FCXM. | Often more sensitive in detecting low-level antibodies. |
Specificity | Detects both HLA/non-HLA antibodies. | Detects both HLA/non-HLA antibodies. |
Quantification | Qualitative assessment. | Quantitative to semi-quantitative |
Advantages | Simplicity and lower cost. | Higher sensitivity, specificity, and ability to quantify antibody binding. |
Disadvantages | Limited sensitivity and specificity. | Potentially higher cost and complexity |
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Mishra, V.C.; Chandra, D.; Raina, V. Histocompatibility Testing: A Fundamental Aspect of Renal Transplant Workup. Transplantology 2024, 5, 85-97. https://doi.org/10.3390/transplantology5020009
Mishra VC, Chandra D, Raina V. Histocompatibility Testing: A Fundamental Aspect of Renal Transplant Workup. Transplantology. 2024; 5(2):85-97. https://doi.org/10.3390/transplantology5020009
Chicago/Turabian StyleMishra, Vikash Chandra, Dinesh Chandra, and Vimarsh Raina. 2024. "Histocompatibility Testing: A Fundamental Aspect of Renal Transplant Workup" Transplantology 5, no. 2: 85-97. https://doi.org/10.3390/transplantology5020009