Functional versus structural matching: can the CTLp test be replaced by HLA allele typing?

Area of Science:

• Immunogenetics
• Transplantation Immunology
• Molecular Biology

Background:

• Human leukocyte antigen (HLA) incompatibilities pose significant immunological barriers in unrelated donor bone marrow transplants.
• Traditional donor selection involved serological HLA class I and DNA-based HLA class II typing.
• Cytotoxic T-lymphocyte precursor (CTLp) assays have been integral to donor selection at our center.

Purpose of the Study:

• To investigate the correlation between HLA class I incompatibilities and CTLp frequencies in donor-recipient pairs.
• To evaluate the utility of CTLp assays in identifying permissible HLA mismatches for bone marrow transplantation.

Main Methods:

• DNA-based typing for HLA class I (HLA-A, -B, -C) in 211 donor-recipient pairs.
• Assessment of CTLp frequencies against HLA incompatibilities.
• Analysis of HLA amino acid sequences in HLA-C mismatched pairs.

Main Results:

• Significant association (p < 0.001) between HLA class I incompatibilities and high CTLp frequencies.
• Exceptions noted: 14% of matched pairs had high CTLp, and 7% of mismatched pairs had low CTLp.
• HLA-C mismatches showed varied CTLp outcomes; amino acid differences in the peptide-binding groove correlated with high CTLp frequencies.

Conclusions:

• A strong correlation exists between CTLp frequency test results and HLA class I typing, but exceptions warrant further investigation.
• The CTLp assay shows potential as a tool to identify permissible mismatches when no fully matched donor is available.
• Further research is needed to determine the clinical relevance of observed exceptions and their impact on allograft recognition.