RARE HLA ALLELES AND IMPACT ON HLA-MATCHING IN KIDNEY TRANSPLANTATION.

Aim: In kidney transplant candidates an increase of the rare HLA alleles due to immigration flow growth was observed. The high polymorphism of HLA alleles should make difficult the finding a suitable donor, especially in sensitized patients. In fact, humoral immune response often determines the production of a broad antibodies pattern due to the recognition of mismatched HLA epitopes. Methods: We analyzed the presence of rare HLA alleles in 934 renal transplant candidates, routinely typed by SSP/-rSSO method and, on the basis of HLA antibody identification, the typing was enlarged to pertinent HLA loci. Rare alleles were confirmed by high resolution SSP method. The allele frequencies (af) were assessed by direct count and the potential immunogenic epitopes were assessed comparing amino acid sequences of these alleles with the corresponding alleles by an online database. Results: A total of 20 rare alleles (2.1%) was found and some of these are give below: B/14:06:01 (af = 1.96%, Caucasian patient), differs from other B/14 alleles by Tryptophan?Arginine substitution at position 97; B/15:38 (af = 1.00%, Asian patient), differs from other B/15 alleles by Histidine?Tyrosine substitution at position 171; B/18:18, (af = 0.58%, Caucasian patient), differs from other B/18 alleles by Serine?Tyrosine substitutions at position 99; B/51:07 (af = 0.58%, Caucasian patient), differs from other B/51 alleles by Serine? Phenylalanine substitution at position 67; DRB1/14:16 (af = 0.93%, Caucasian patient) differs from other DRB1/14 alleles by Leucine?Isoleucine, Arginine?Aspartic acid, Arginine?Glutamic acid, Glutamic acid?Alanine substitutions at positions 67, 70, 71, 74; DQB1/03:05 (af = 0.88%, Caucasian patient), differs from other DQB1/03 alleles by Leucine?Glycine substitution at position 26. Conclusions: The presence of rare HLA alleles suggests a new policy of HLA typing providing amino acid sequence information and the application of an epitope-based HLA-matching to improve clinical course of kidney transplantation.