HLA Typing and Matching in Solid Organ Transplantation

Importance of HLA Matching

HLA antigen determination is decisive for donor‑recipient matching in solid‑organ transplantation, guiding allocation and reducing rejection risk. 1
Each HLA mismatch at HLA‑A, ‑B, ‑C, and ‑DRB1 reduces graft survival by approximately 5–10% depending on the recipient’s disease‑risk profile. 2

Kidney transplantation: High‑resolution (2‑field) HLA genotyping for HLA‑A, ‑B, ‑C, ‑DRB1, and DQB1 is recommended with Grade 1A evidence. 1
Heart transplantation: High‑resolution HLA genotyping is recommended with Grade 1B evidence. 3
Lung transplantation: High‑resolution HLA genotyping is recommended with Grade 1B evidence. 3
Liver transplantation: High‑resolution HLA genotyping is recommended with Grade 2C evidence. 1

High‑resolution testing of HLA‑A, ‑B, ‑C, and ‑DRB1 should be performed on all potential donors to optimize compatibility. 4
Inclusion of HLA‑DQB1 typing is increasingly critical; each HLA‑DQ mismatch raises the hazard ratio for graft loss by ~1.12. 5
Over 50 % of long‑term kidney graft failures are attributable to donor‑specific antibody (DSA)–mediated rejection. 6
Between 54 % and 77 % of patients who develop de novo DSA generate antibodies against HLA‑DQ, which are strongly associated with antibody‑mediated rejection and graft loss. 2

Both HLA‑DQA1 and HLA‑DQB1 chains must be assessed as heterodimers because each contributes to immunogenicity. 5
Luminex‑based platforms provide sufficient resolution to eliminate most common ambiguities in solid‑organ HLA typing. 5
Allele‑level (high‑resolution) typing is superior to antigen‑level typing for accurate compatibility assessment. 4

Do not rely solely on antigen‑level matching when allele‑level differences exist (e.g., B44:02 vs. B44:03). 7
Do not neglect HLA‑DQ matching; omission is linked to poorer long‑term outcomes. 5
Do not ignore the need to evaluate both HLA‑DQA1 and HLA‑DQB1 chains when assessing DQ compatibility. 5

Patients without a spleen have a markedly increased risk of infection with encapsulated bacteria, particularly Streptococcus pneumoniae and Neisseria meningitidis; Haemophilus influenzae is less commonly the primary pathogen. 4
Routine splenectomy in transplant recipients has been largely abandoned because its efficacy is unclear and it is associated with serious adverse events, including death and infectious complications. 8

High‑resolution allele‑level HLA‑B typing is required for kidney transplantation because different alleles within the same serologic family have distinct immunogenicity and vary in frequency across ethnic groups. 9
In Caucasian populations, allele B*08:01 occurs in about 12.5 %, versus 3.8 % in African‑American populations; the HLA‑B44 serologic group includes B*44:02 (≈9 %) and B*44:03 (≈5 %) in White individuals, which cannot be distinguished without allele‑level typing. 9
Accurate donor‑recipient matching and identification of donor‑specific antibodies depend on allele‑level HLA‑B typing; antigen‑level typing cannot determine the precise degree of mismatch. 9

Luminex‑based HLA typing platforms deliver sufficient resolution to resolve most common ambiguities, are considerably less expensive than sequencing, and are already widely implemented in clinical laboratories. 9

Antigen‑level typing alone is insufficient because allele‑specific differences (e.g., B44:02 vs. B44:03) have distinct clinical implications that are missed without high‑resolution typing. 9
HLA‑B allele frequencies differ markedly among ethnic groups, influencing matching probabilities and the cost‑effectiveness of screening strategies; assuming uniform frequencies can lead to suboptimal transplant outcomes. 9