Donor-specific antibody against denatured HLA-A1: clinically nonsignificant?

Area of Science:

• Nephrology
• Immunology
• Transplantation immunology

Background:

• Pre-transplant screening for human leukocyte antigen (HLA) alloantibodies is crucial for kidney transplant success.
• Standard methods like anti-human globulin-complement-dependent cytotoxicity (AHG-CDC) and enzyme-linked immunosorbent assay (ELISA) are used for antibody detection.

Observation:

• A kidney transplant recipient with end-stage renal disease (ESRD) showed no detectable anti-HLA antibodies pre-transplant using standard assays.
• Post-transplant, single antigen (SA) array screening revealed reactivity against the donor's HLA-A1 antigen.
• Despite this reactivity, the patient exhibited excellent graft function and no evidence of rejection at 5 years post-transplant.

Findings:

• The detected anti-A1 antibodies showed significantly higher reactivity with denatured HLA-A1 antigens compared to native antigens.
• Flow cytometric crossmatches (FXM) using both native and denatured cells were negative, suggesting the antibodies targeted denatured epitopes.
• These findings indicate the presence of antibodies reacting with denatured human leukocyte antigens, which may not be clinically relevant for graft rejection.

Implications:

• Bead-based screening assays may produce false positives due to antibodies recognizing denatured HLA antigens.
• Antibodies detected by SA arrays that are negative in flow cytometric crossmatches may not pose a risk for humoral rejection.
• Further investigation of such antibodies is warranted to avoid unnecessary barriers to transplantation and improve patient outcomes.