Antibodies against HLA-DP recognize broadly expressed epitopes

Area of Science:

• Immunogenetics
• Transplantation immunology
• Serology

Background:

• Human Leukocyte Antigen (HLA) matching and pre-transplant donor-specific antibody (DSA) avoidance are critical for solid organ transplant (SOT) success.
• Solid-phase testing using single antigen beads (SAB) enables precise antibody reactivity assessment at the allele level.

Purpose of the Study:

• To analyze selective reactivity patterns of anti-HLA antibodies, particularly anti-HLA-DP antibodies, using SAB testing data from a large transplant center.
• To investigate the epitope targets of anti-HLA-DP antibodies and their clinical relevance.

Main Methods:

• Retrospective review of SAB testing results from a large transplant center.
• Identification and characterization of anti-HLA antibody reactivity patterns, focusing on HLA-DP.
• Correlation of HLA-DP antibody reactivity with B cell flow crossmatch outcomes.

Main Results:

• Anti-HLA-DP antibodies were frequently detected, sometimes in isolation.
• Two out of nine sera with HLA-DP antibodies showed positive B cell flow crossmatch results.
• Reactivity patterns often mapped to hypervariable regions C and F of DPB1, but also to other DPB1 regions and DPA1.
• Analysis indicated that anti-HLA-DP antibodies predominantly recognize broadly cross-reactive epitopes.

Conclusions:

• Anti-HLA-DP antibodies exhibit a predominant pattern of recognizing broadly cross-reactive epitopes.
• HLA-DP typing is now mandated for deceased kidney donors by the United Network for Organ Sharing.
• HLA-DP epitopes should be prioritized as major antigens for DSA avoidance strategies in transplantation.