NIV Congres
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Predicted Indirectly Recognizable HLA epitopes presented by HLA-DRB1 correlate with the de novo development of donor-specific HLA IgG antibodies after kidney transplantation
Otten, H.G., Calis, J.J.A., Kesmir, C., Zuilen, A.D. van, Spierings, E.
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Background HLA class-I mismatches selectively induce antibody formation after kidney transplantation. The de novo development of donor-specific IgG HLA class-I antibodies may be dependent on the HLA class-II background of the patient by presenting T-helper epitopes within the recognized HLA class-I antigens. Methods. The correlation between antibody production against mismatched donor human leukocyte antigens (HLA) class I and the number of HLA class II-restricted predicted indirectly recognizable HLA epitopes (PIRCHE-IIs) in the respective HLA class-I mismatches was investigated. To this end, we analyzed sera taken after nefrectomy from a cohort of 21 non-immunized individuals that received and rejected a renal transplant Results. Fourty-nine HLA class-I mismatches were found which all contained immunogenic eplets according to HLA-Matchmaker. Donor specific HLA antibody responses were detected against 38 HLA class-I mismatches after nefrectomy. These mismatches were found to contain a larger number of PIRCHE-IIs when compared to mismatches which did not induce donor specific HLA antibodies. Most PIRCHE-IIs (more than 60%) were not part of an eplet as defined by HLA-Matchmaker.
Conclusions Our data suggest that presentation of donor-derived HLA class-I peptides by recipient HLA class-II molecules plays a significant role in de novo development of donor-specific IgG HLA antibodies.