engleski

PREDICTING THE IMMUNOGENICITY OF HLA MISMATCHED ANTIGENS IN PATIENT AWAITING THIRD RENAL TRANSPLANTATION APPLYING THE HLAMATCHMAKER AND PIRCHE ALGORITHM

HLA mismatches between donor and recipient frequently lead to production of HLA-specific antibodies. The HLAMatchmaker is a computer algorithm that compares HLA compatibility at the structural level and considers each HLA specificity as multiple linear triplet-defined epitopes to identify the number of shared and nonshared epitopes between donor and recipient. The PIRCHE-II (predicted indirectly recognizable HLA epitopes) is another algorithm which predicts donor-HLA-derived peptides presented by the recipient’s HLA-DRB1 molecules which may be detected by the patients’ T cells. It has been shown that the result score of both algorithms correlate with the risk of HLA donor-specific antibodies (DSA) development. This case present prediction of immunogenicity and the risk of DSA formation based on the mismatched (MM) HLA antigens between cadaveric donor and patient waiting the third kidney transplantation, using HLAMatchmaker and PIRCHE-II algorithm. The patient is 38 years old male who recieved first kidney graft from living donor in 2007 (ABDR MM 000), and only two months later was re-transplanted with the kidney from the second living donor (ABDR MM 011). At the time of returning to the waiting list in 2017, the antibody profile of the patient, determined by Luminex LSA class I and class II Single Antigens beads (SA1, SA2), was negative for antibodies against HLA class I antigens and positive for the presence of HLA class II antibodies (DR1, DR7, DR9, DR10, DR15, DR16, DR51, DR53, DQ8, DQ9, DQA1*03) among which there were DSAs against the second donor: DR53 (MFI 6100), DQ8 (MFI 2200-3400) and DQA1*03 (MFI 2600-3800 ). In October 2017, the patient received kidney offer from cadaveric donor and the chance for the third transplantation. The donor/patient ABCDRDQ MM was 12200, with Luminex SA1, SA2 testing results negative for all ABCDRDQ MM antigens. Patient's and potential third donor's HLA-A, -B, -C, -DRB1 and DQB1 alleles, determined at low resolution level, were assigned to the most common corresponding four digit HLA allele and were entered into the HLAMatchmaker program (version 02) to determine the number of donor eplets that were absent in the patient as well as in the PIRCHE-II algorithm (version 2.4.21) to predict the presentation of HLA-derived mismatched peptide by the patient’s HLA-DRB1 molecules. The donor and patient were mismatched for HLA-A3, B27, B35, Cw2 and Cw4 antigens. The HLAMatchmaker analysis revealed 12 epitopes in total differing beetwen donor and the patient among which only 5 epitopes were „Antibody-verified Epitopes“ (AbVerEp ; identified experimentally with informative HLA antibodies). The PIRCHE-II score was 29. According to Lachmann et al. patients with a HLAMatchmaker score ≥5 to <18 have a predicted incidence of DSA of 13.4% and patients with a PIRCHE-II score ≥9 to <35 have a predicted incidence of DSA of 13.1%. So in case of our patient, predicted immunogenicity of a HLA MM antigens and risk of developing DSA is low. The HLAMatchmaker and PIRCHE-II algorithms can serve as additional tool in allocation of donor organs to patients with decreased immunological risk for DSA formation following kidney transplantation.

IMMUNOGENICITY OF HLA MISMATCHED ANTIGENS, HLAMATCHMAKER, PIRCHE

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