Uncommon HLA Alleles/Haplotypes and HLA-Matching in Renal Transplantation (Abstract/Comunicazione in rivista)

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  • Uncommon HLA Alleles/Haplotypes and HLA-Matching in Renal Transplantation (Abstract/Comunicazione in rivista) (literal)
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  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1097 (literal)
Alternative label
  • Ozzella G.1, Poggi E.1, Mazzitelli L.2, Carducci M.2, Imbroglini V.2, Adorno D.2, Piazza A.1,3 (2012)
    Uncommon HLA Alleles/Haplotypes and HLA-Matching in Renal Transplantation
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  • Ozzella G.1, Poggi E.1, Mazzitelli L.2, Carducci M.2, Imbroglini V.2, Adorno D.2, Piazza A.1,3 (literal)
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  • Transplantation (literal)
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  • 1National Council of Researches, IFT Unit of Rome S. Camillo Hospital, Rome, Italy, 2Tor Vergata University of Rome, Regional Transplant Center-Lazio, Rome, Italy, 3Regional Transplant Center of Lazio, Rome, Italy (literal)
Titolo
  • Uncommon HLA Alleles/Haplotypes and HLA-Matching in Renal Transplantation (literal)
Abstract
  • HLA Antibodies in Organ Transplantation TUE.CO38.04 - Uncommon HLA Alleles/Haplotypes and HLA-Matching in Renal Transplantation Ozzella G.1, Poggi E.1, Mazzitelli L.2, Carducci M.2, Imbroglini V.2, Adorno D.2, Piazza A.1,3 1National Council of Researches, IFT Unit of Rome S. Camillo Hospital, Rome, Italy, 2Tor Vergata University of Rome, Regional Transplant Center-Lazio, Rome, Italy, 3Regional Transplant Center of Lazio, Rome, Italy Introduction: In renal transplantation histocompatibility criteria for donor-recipient HLA-matching classically considers A, B and DR antigens only. But other HLA molecules, like DQ and DP heterodimers, are polymorphic and can elicit a humoral immune response. Moreover, the increase of uncommon HLA alleles and haplotypes, due to immigration flow growth, 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 epitopes shared with several intra/inter HLA molecules. For this reason, in the Regional Transplant Center-Lazio, HLA typings of renal transplant candidates and kidney donor were enlarged to HLA-DQB1 locus. Methods: We analyzed the presence of rare HLA alleles in 934 renal transplant candidates, routinely typed for HLA-A, -B, - DR and -DQ alleles by low resolution PCR-SSP and/or -rSSO methods. Rare alleles were confirmed by high resolution PCRSSP methods. The allele frequencies were assessed by direct count and compared with those reported on online database (www.allelefrequencies.net). The potential immunogenic epitopes of rare alleles were assessed comparing amino acid sequences of these alleles with the common corresponding allele by an online database (www.ebi.ac.uk/imgt/hla). Results: A total of 20 rare alleles (2.1%) was found. A*02:11 alleles (af=0.25%), detected in an Asian patient, differs from other A*02 alleles by Threonine vs Isoleucine substitution at position 73 and Histidine vs Aspartic acid substitution at position 74; B*14:06 (af=1.96%), detected in an Italian patient, differs from other B*14 alleles by Tryptophan vs Arginine substitution at position 97; B*15:38 (af=1.00%), detected in an Asian patient, differs from other B*15 alleles by Histidine vs Tyrosine substitution at position 171; B*44:29, (af=0.75%), detected in an Italian patient, differs from other B*44 alleles by Aspartic acid vs Leucine substitutions at position 156 and Alanine vs Threonine substitutions at position 158; DQB1*03:05 (af=0.29%) detected, in an Italian patient, differs from other B*03 alleles by Leucine vs Glicine substitution at position 26. Based on the haplotype frequencies in Caucasian population, two uncommon HLA DRB1-DQB1 associations were found in Caucasian renal transplant candidates. The first association was DRB1*11:01-DQB1*05:02 (DR11-DQ5 phenotype), the second was DRB1*11:01-DQB1*03:02 (DR11-DQ8 phenotype), while, in Caucasian population, the common linkage was DRB1*11:01-DQB1*03:01 (DR11-DQ7 phenotype). Conclusion: The recognition by the patient immune system of polymorphic substitutions of rare alleles may determine the production of spread antibody pattern, depending on HLA molecules sharing the same epitope, with a deleterious impact on kidney graft outcome. Our findings suggest new policy of HLA typing and the application of an epitope-based HLA matching to improve both kidney allocation and clinical graft outcome. All abstracts are available in a quotable version on the Transplantation Journal Website www.transplantjournal.com from beginning of September 2012 (literal)
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