E. Longhi

Epidemiologic study on the origin of cancer after kidney transplantation.

Background. Subjects who underwent solid organ transplantation are at higher risk for a wide variety of cancers. Methods. The authors investigated the origin of cancer in a cohort of 2,526 patients followed up for 60.7±35.6 months after kidney transplantation between 1990 and 2000 in seven transplant centers. Results. One hundred four of them developed cancer. All subjects who developed solid cancer within 6 months after transplantation (n=10) and a group of subjects who developed solid cancer after 6 months posttransplant (n=10) were selected. Short tandem repeat analysis was performed on paraffin-embedded biopsy specimens of tumors and on both donor and recipient pretransplant peripheral blood. Biologic material was obtained in 17 of the 20 selected patients (85.0%). The analysis showed that 16 of 17 tumors were genetically identical to the recipient. Conclusions. The authors’ results suggest that donor transmission of solid cancer is an unlikely event in their population.

Description and molecular modeling of two novel HLA alleles: HLA-A*0343 and A*0345

We report the identification of two novel human leucocyte antigen (HLA) in two Caucasian individuals. HLA-A*0343 differs from A*03010101 by four changes at nucleotides 411-414 (CCGG-->TGAA) and by a point mutation at position 418 (G-->C). These differences lead to two amino acid substitutions at codon 114, where arginine has changed into negatively charged glutamic acid, and at codon 116, where aspartic acid has changed into positively charged histidine. Molecular modeling showed that these changes have a profound influence on the overall charge of the F pocket of the groove, resulting in potentially important changes in the peptide repertoire. HLA-A*0345 was found in a hematological female patient candidate to bone marrow transplantation. This new variant differs from HLA-A*03010101 at position 845 (C-->A) encoding an amino acid change of threonine to asparagine at codon 258 located in the alpha3 domain. Molecular modeling does not suggest a substantial role of this substitutions on the interaction with beta2-microglobulin or CD8.

Identification of two novel HLA-DRB1*11 alleles (DRB1*110404 and DRB1*1161) in two Italian cord blood units

We describe the isolation and characterization of two novel HLA‐DRB1*11 alleles, officially named DRB1*1161 and 110404. These two new variants were both identified in two Caucasoid individuals. The exon 2 sequence of DRB1*1161 is identical to that of DRB1*110101 except at codon 41, where a nucleotide substitution (GAC>AAC) is responsible for an amino‐acidic change from Asp to Asn. The exon 2 sequence of the second novel allele described here, DRB1*110404, differs from that of DRB1*110401 only at codon 34 where the nucleotidic change CAA>CAG gives rise to a silent mutation.

A novel HLA-B*18:80 allele identified by SBT typing in an Italian bone marrow volunteer donor.

A novel allele, officially named B*18:80, was detected in a Caucasoid individual by polymerase chain reaction–sequence‐specific primers and SBT. The new allele differs from B*18:01:01 at two nucleotidic positions in codon 24 at exon 2.

Description of the new allele HLA-DQB1*04:03:02.

A new variant of HLA‐DQB1*04:03 allele officially designated as HLA‐DQB1*04:03:02 was detected in two unrelated Caucasoid individuals by polymerase chain reaction‐sequence‐specific primers and SBT. The new allele nucleotide sequence differs from HLA‐DQB1*04:03:01 for a single silent point mutation in exon 2 at position 159, codon 21.

Three novel alleles at the HLA-DRB1 locus identified by sequence-based typing.

We describe here the sequences of 3 new HLA-DRB1 variants officially named DRB1*03:05:03, DRB1*11:10:02, and DRB1*14:86. These novel alleles have been detected in 3 Caucasoid individuals by sequence-based typing. The first and second alleles are the result of a silent mutation, which does not imply any amino acid change. The sequence of DRB1*14:86 exhibits a single nucleotide difference with the allele DRB1*14:01:01 at position 239.

Description and molecular modeling of a novel human leukocyte antigen allele: A*32:22

We describe here the sequence and the molecular modeling of a new variant of HLA-A*32 allele officially named A*32:22. This novel allele has been detected in an Italian cord blood sample by sequence-based typing (SBT). The mutation (CAT →CGT), which has occurred at codon 151, at nucleotide position 524, implies an amino acidic change from Histidine to Arginine. Residue 151 is located on top of the molecule inside the region contacted by T cell receptor (TCR) and it is possibly involved in docking TCR. A positively charged residue is maintained on this position determining a slight change of electrostatic potential on the molecular surface. This suggests a limited functional relevance of the amino acid substitution encoded by A*32:22.

Identification of two new HLA-DRB1 alleles, DRB1*040405 and DRB1*1190.

We describe here two novel DRB1 alleles, officially named *040405 and *1190. DRB1*040405 differs from DRB1*0404 for one point mutation at codon 72 with no coding changes. DRB1*1190 is identical to DRB1*110101 except for a nucleotide substitution at codon 24 which causes an aminoacidic mutation from valine to methionine. Over time we have been witnessing the identification of a great number of new HLA alleles. DRB1 allelic variability is mostly present in the second exon and more that 760 alleles have been so far identified. Here, we report the description of two novel DRB1 alleles, named *040405 and *1190, and identified in two Caucasoid subjects.

Characterization of two novel HLA class I alleles: HLA-A*310103 and HLA-B*9531.

Two novel human leucocyte antigen (HLA) class I alleles were characterized by means of sequencing‐based typing techniques. HLA‐A*310103 was identified in a cord blood unit from a Caucasoid individual. The sequence of this allele is identical to that of HLA‐A*310102 except for a silent mutation in exon 3 at position 480 (G → A). HLA‐B*9531 was found in a Caucasoid female patient registered on the heart transplantation waiting list in the North Italy Transplant programme. This new variant differs from HLA‐B*1503 at position 572 (G → C) in exon 3. This nucleotide change leads to an amino acidic substitution at codon 167 from tryptophan to serine.

Molecular modelling of HLA-B*35:132.

Here we describe the molecular modelling of the new variant HLA‐B*35:132. This allele shows one mismatch with B*35:01:01:01 in exon 3 at position 575 where a T is substituted by a C, which implies an amino acidic change from Leucine to Proline. This seems not to alter the molecular structure and not to compromise the HLA complex and T‐cell receptor interaction.