The role of DRB1 amino acid residue differences on donor-specific antibody production and acute rejection after cadaveric renal transplant.
The correlation between DRB1 amino acid residue matching, post-transplant humoral response and acute rejection (ARj) episodes was analysed in 51 renal transplant donor-recipient pairs in order to determine new criteria for organ assignment based on the alloreactivity of the residue within the peptide binding groove. HLA class I and II compatibility was defined using serological and genomic techniques; a sequence-based typing (SBT) was used for a higher resolution of DRB1 alleles. Humoral response was monitored in the first post-transplant year using triple staining flow cytometric analysis of donor-specific antibodies (Abs). Our data showed that DRB1 residue compatibility was always correlated to the absence of ARj while the presence of one or more aminoacid differences was associated with a similar frequency of ARj. Analysis of the mismatched DRB1 amino acid residue localised in the beta-pleated sheet and the alpha-helix of the DRB 1 molecule revealed that the frequency of beta-pleated sheet residue mismatches (MMs) was higher in the ARj-positive than in the ARj-negative group. A significant increase in the alpha-helix residue MMs was observed in patients with anti-class II Ab production (p = 0.034). Furthermore, analysing in detail DRB 1 MMs at the level of single amino acid residue, we found that the frequency of the mismatches localized in codon 9 and codon 28 in the beta-pleated sheet, as well as in codon 57 in the alpha-helix, was higher in patients who experienced ARj; on the other hand, MMs in codon 58 of the alpha-helix were more frequently associated with anti-class II Ab production. The identification of the residues more involved in alloreactivity onset will make it possible to define the existence of "permissive" or immunogenic" allele combinations which could simplify and increase the chances of a successful transplant.
Adorno
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Istituto CNR, Tipizzazione Tissutale e Problemi della Dialisi, L'Aquila, Italy. D.Adorno@area.ba.cnr.it
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Valeri
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Torlone
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Monaco
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Papola
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Casciani
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D000596:Amino Acids / Q000032:analysis; D000917:Antibody Formation; D002102:Cadaver; D003062:Codon; D005260:Female; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D017422:Sequence Analysis, DNA
D000596:Amino Acids; D003062:Codon; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains