Simultaneous Living Donor Kidney and Parathyroid Allotransplantation: First Case Report and Review of Literature.

BACKGROUND: Congenital hypoparathyroidism can be severely debilitating for patients, leading to renal failure at young age. Parathyroid transplantation may represent a permanent parathyroid replacement therapy. In patients already on immunosuppression for other organ transplant, there is little additional risk involved with parathyroid allotransplantation. METHODS: Robotic assisted transaxillary single parathyroidectomy is performed on a living donor also donating a kidney to her sibling. RESULTS: Recipient total serum PTH levels became detectable after 3 days from the procedure and maintained for 9 months after transplant with minimal calcium supplementation after the procedure. Literature review and previous results are summarized. CONCLUSIONS: Obtaining a parathyroid gland and a kidney from the same donor reduces the exposure to different HLA antigens. The combined procedure using minimally invasive surgery is safe, with the additional cosmetic advantage and convenience for the willing donor. In the setting of need for immunosuppression, additional transplantation to treat the cause is safe and justified in the recipients.

EpicCapo: epitope prediction using combined information of amino acid pairwise contact potentials and HLA-peptide contact site information.

BACKGROUND: Epitope identification is an essential step toward synthetic vaccine development since epitopes play an important role in activating immune response. Classical experimental approaches are laborious and time-consuming, and therefore computational methods for generating epitope candidates have been actively studied. Most of these methods, however, are based on sophisticated nonlinear techniques for achieving higher predictive performance. The use of these techniques tend to diminish their interpretability with respect to binding potential: that is, they do not provide much insight into binding mechanisms. RESULTS: We have developed a novel epitope prediction method named EpicCapo and its variants, EpicCapo(+) and EpicCapo(+REF). Nonapeptides were encoded numerically using a novel peptide-encoding scheme for machine learning algorithms by utilizing 40 amino acid pairwise contact potentials (referred to as AAPPs throughout this paper). The predictive performances of EpicCapo(+) and EpicCapo(+REF) outperformed other state-of-the-art methods without losing interpretability. Interestingly, the most informative AAPPs estimated by our study were those developed by Micheletti and Simons while previous studies utilized two AAPPs developed by Miyazawa & Jernigan and Betancourt & Thirumalai. In addition, we found that all amino acid positions in nonapeptides could effect on performances of the predictive models including non-anchor positions. Finally, EpicCapo(+REF) was applied to identify candidates of promiscuous epitopes. As a result, 67.1% of the predicted nonapeptides epitopes were consistent with preceding studies based on immunological experiments. CONCLUSIONS: Our method achieved high performance in testing with benchmark datasets. In addition, our study identified a number of candidates of promiscuous CTL epitopes consistent with previously reported immunological experiments. We speculate that our techniques may be useful in the development of new vaccines. The R implementation of EpicCapo(+REF) is available at http://pirun.ku.ac.th/~fsciiok/EpicCapoREF.zip. Datasets are available at http://pirun.ku.ac.th/~fsciiok/Datasets.zip.

Structural epitope matching for HLA-alloimmunized thrombocytopenic patients: a new strategy to provide more effective platelet transfusion support?

BACKGROUND: During the past three decades, HLA matching for platelet (PLT) transfusion of refractory thrombocytopenic patients has been based on serologic cross-reactivity between HLA-A and HLA-B antigens. Although many blood banks are using this matching strategy, the general experience is that such matched PLT transfusions are often ineffective. STUDY DESIGN AND METHODS: This report describes a new HLA matching algorithm that considers structurally defined epitopes recognized by antibodies. HLAMatchmaker is a computer program that determines histocompatibility at the amino acid level initially designed as triplets (i.e., linear sequences of three residues in molecular surface-exposed positions) but now updated as eplets representing patches of antibody-accessible polymorphic residues surrounded by residues within a 3-A radius. The eplet version of HLAMatchmaker is also useful in the analysis of HLA antibody reactivity patterns of alloimmunized patients so that acceptable mismatches can be identified. CONCLUSION: An HLA epitope-based matching protocol is proposed that may permit a more effective PLT transfusion management of refractory patients. This protocol includes high-resolution HLA-A, -B, and -C typing of patients and donors, serum screening to identify acceptable mismatches, and the identification of suitable donors in a donor database that incorporates HLAMatchmaker as a search engine. HLAMatchmaker programs can be downloaded from the Web site http://tpis.upmc.edu/tpis/HLAMatchmaker/.

The crystal structures of the oligopeptide-binding protein OppA complexed with tripeptide and tetrapeptide ligands.

BACKGROUND: The periplasmic oligopeptide-binding protein OppA has a remarkably broad substrate specificity, binding peptides of two or five amino-acid residues with high affinity, but little regard to sequence. It is therefore an ideal system for studying how different chemical groups can be accommodated in a protein interior. The ability of the protein to bind peptides of different lengths has been studied by co-crystallising it with different ligands. RESULTS: Crystals of OppA from Salmonella typhimurium complexed with the peptides Lys-Lys-Lys (KKK) and Lys-Lys-Lys-Ala (KKKA) have been grown in the presence of uranyl ions which form important crystal contacts. These structures have been refined to 1.4 A and 2.1 A, respectively. The ligands are completely enclosed, their side chains pointing into large hydrated cavities and making few strong interactions with the protein. CONCLUSIONS: Tight peptide binding by OppA arises from strong hydrogen bonding and electrostatic interactions between the protein and the main chain of the ligand. Different basic side chains on the protein form salt bridges with the C terminus of peptide ligands of different lengths.