Insulin-degrading enzyme (IDE): a novel heat shock-like protein.

Insulin-degrading enzyme (IDE) is a highly conserved zinc metallopeptidase that is ubiquitously distributed in human tissues, and particularly abundant in the brain, liver, and muscles. IDE activity has been historically associated with insulin and ß-amyloid catabolism. However, over the last decade, several experimental findings have established that IDE is also involved in a wide variety of physiopathological processes, including ubiquitin clearance and Varicella Zoster Virus infection. In this study, we demonstrate that normal and malignant cells exposed to different stresses markedly up-regulate IDE in a heat shock protein (HSP)-like fashion. Additionally, we focused our attention on tumor cells and report that (i) IDE is overexpressed in vivo in tumors of the central nervous system (CNS); (ii) IDE-silencing inhibits neuroblastoma (SHSY5Y) cell proliferation and triggers cell death; (iii) IDE inhibition is accompanied by a decrease of the poly-ubiquitinated protein content and co-immunoprecipitates with proteasome and ubiquitin in SHSY5Y cells. In this work, we propose a novel role for IDE as a heat shock protein with implications in cell growth regulation and cancer progression, thus opening up an intriguing hypothesis of IDE as an anticancer target.

Identification of the novel HLA-C*07:852 allele by sequencing-based typing.

The new allele HLA-C*07:852 differs from HLA-C* 07:04:01:01 by one nucleotide substitution in codon 314 in exon 5.

Identification of the novel allele HLA-DQB1*06:02:61 by next-generation sequencing.

HLA-DQB1*06:02:61 differs from HLA-DQB1*06:02:01:01 by one nucleotide substitution in exon 4-5512 G>A.

Characterisation of the novel HLA-DRB3*02:202 allele by sequencing-based typing.

HLA-DRB3*02:202 differs from DRB3*02:112 by one nucleotide substitution in codon 51 in exon 2.

Role of HLA in cardiothoracic transplantation.

In current clinical practice, transplant clinicians create collaborative working relationships with histocompatibility laboratory scientists to identify the risk of long-term graft failure, which may assist in establishing strategies for treatment and surveillance. Transplant immunology research also focuses on optimizing human leukocyte antibody tissue typing and defines the most effective test for detecting the presence of donor-specific antibodies. Although several studies have been conducted, data on pediatric heart transplant recipients are limited. Epitope load information may be utilized to identify donors with permissible human leukocyte antibody mismatches to increase transplant success. Although current guidelines do not consider human leukocyte antibody epitope-based matching tools, these guidelines could be useful for identifying recipients at a high risk of donor-specific antibody production, which would be appropriate for routine donor-specific antibody screening to initiate early interventions to prevent antibody-mediated rejection. Human leukocyte antibody matching at the epitope level offers an effective approach for identifying acceptable mismatches in sensitized patients and provides information about epitope loads. In the future, eplet matching may be used to define the best immunosuppressive therapy protocol for cardiothoracic organ transplantation. This report provides an overview of the role of human leukocyte antibodies in heart and lung transplantation.

Identification of the novel HLA-A*02:01:189 allele.

HLA-A*02:01:189 differs from HLA-A*02:01:01:01 by one nucleotide substitution in Exon 3, codon 101 TGC > TGT.

Identification of the novel HLA-DPA1*01:149 allele by next-generation sequencing.

The novel HLA-DPA1*01:149 allele differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in exon 2.

Identification of the novel HLA-DPA1*02:110:02 allele by next-generation sequencing.

The novel HLA-DPA1*02:110:02 allele differs from HLA-DPA1*02:01:01:06 by one nucleotide substitution in exon 4.

Characterization of the novel HLA-DRB1*11:04:21 allele by sequencing-based typing.

HLA-DRB1*11:04:21 differs from HLA-DRB1*11:04:01 by one nucleotide substitution in codon 69 in exon 2.

Characterization of the novel HLA-DQA1*01:89 allele by sequencing-based typing.

HLA-DQA1*01:89 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in codon -5 in exon 1.

Characterization of the novel HLA-DQA1*01:76 allele by sequencing-based typing.

HLA-DQA1*01:76 differs from HLA-DQA1*01:03:01:06 by one nucleotide substitution in codon -11 in exon 1.

Identification of the novel HLA-DPA1 allele, DPA1*02:53 by next-generation sequencing.

The novel HLA-DPA1*02:53 allele differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in exon 3.

A new HLA-B allele, HLA-B*07:422.

The novel allele HLA-B*07:422 differs from HLA-B*07:02:01:01 by one nucleotide substitution in exon 4.

Identification of the novel HLA-A*30:181 allele by next-generation sequencing.

HLA-A*30:181 differs from HLA-A*30:01:01 by one nucleotide substitution in Exon 4832 G to A.

Characterization of the novel HLA-DQA1*03:20 allele by sequencing-based typing.

HLA-DQA1*03:20 differs from HLA-DQA1*03:03:01:01 by one nucleotide substitution in codon 33 in exon 2.

Identification of a new HLA-B*44 allele, HLA-B*44:02:68, by next generation sequencing.

HLA-B*44:02:68 differs from B*44:02:01:01 by one synonmous nucleotide substitution in codon-10 GGG- > GGA.