• MeSH
• Diagnostic Techniques, Cardiovascular MeSH
• Health Care Economics and Organizations MeSH
• Cachexia etiology   MeSH
• Cardio-Renal Syndrome etiology   MeSH
• Contraindications, Procedure MeSH
• Humans MeSH
• Heart-Assist Devices MeSH
• Disease Progression * MeSH
• Ventricular Remodeling MeSH
• Liver Failure etiology   MeSH
• Heart Failure * complications   MeSH
• Histocompatibility Testing methods   MeSH
• Heart Transplantation methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Protilátkami zprostředkovaná (humorální) rejekce je závažná komplikace, která je asociována se zhoršenou prognózou přežití transplantovaných orgánů. Její diagnostika byla dlouho zaměřena na detekci protilátek specifických proti HLA antigenům, nicméně se v posledních letech ukázalo, že při rozvoji této rejekce mohou hrát roli i protilátky proti antigenům, které jsou kódovány geny mimo HLA komplex. Non HLA antigeny jsou polymorfní molekuly, a proto mohou být rozpoznány imunitním systémem příjemců orgánů. Tyto antigeny se vyskytují na povrchu endoteliálních a epiteliálních buněk, ale mohou být lokalizovány i intracelulárně a uvolňovat se v případě buněčné lýze. Mezi non HLA antigeny patří molekuly MICA – major-histocompatibility-complex (MHC) class I-related chain A, receptor angiotensinu II-R1, kolagen, K-α1 tubulin, srdeční myosin, vimentin a další. Non HLA protilátky se mohou vyskytovat před transplantací, ale rovněž mohou být produkovány i de novo. Diagnostika non HLA protilátek se provádí za využití xMap technologie (Luminex) nebo endoteliálním crossmatch (křížová zkouška) a dalšími technikami. Nicméně všechny metodiky i interpretace výsledků non HLA má svá úskalí.

Antibody-mediated (humoral) rejection (AMR) is a serious complication that is associated with a worse prognosis of survival of transplanted organs. The diagnosis of AMR has been long time focused on the detection of antibodies specific to HLA antigens, however, in recent years it has become clear that antibodies against antigens encoded by genes outside the HLA complex can also play a role in the development of AMR. Non-HLA antigens are polymorphic molecules and therefore can be recognised by the immune system of organ transplant recipients. These antigens are expressed on the surface of endothelial and epithelial cells, but can also be localised intracellularly and released in case of cell lysis. Non-HLA antigens include molecules MICA – major-histocompatibility-complex (MHC) class I-related chain A, angiotensin II-R1 receptor (ATR1), collagen, K-α1 tubulin, cardiac myosin, vimentin and others. Non-HLA antibodies can occur before transplantation, but may also be produced de novo. The diagnosis of non-HLA antibodies is carried out using xMap technology (Luminex), the so-called endothelial crossmatch and other techniques, however, all methodologies and interpretation of results have their pitfalls.

• Keywords
• non HLA protilátky, technologie Luminex,
• MeSH
• Autoantibodies classification   adverse effects   toxicity   MeSH
• HLA Antigens * immunology   MeSH
• Humans MeSH
• Graft Rejection diagnosis   etiology   complications   MeSH
• Histocompatibility Testing methods   MeSH
• Organ Transplantation MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• Keywords
• non HLA protilátky, technologie Luminex,
• MeSH
• Autoantibodies * classification   adverse effects   toxicity   MeSH
• HLA Antigens immunology   MeSH
• Humans MeSH
• Graft Rejection diagnosis   etiology   complications   MeSH
• Histocompatibility Testing methods   MeSH
• Organ Transplantation * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor available in the deceased donor pool of their allocation organisation and therefore they wait a very long time before being offered a kidney for transplant. Especially patients with rare HLA phenotypes in relation to the actual donor pool are waiting extremely long. As HLA phenotypes are different in the various European populations, we hypothesized that extension of the donor pool outside the respective allocation system will increase the chance of receiving a compatible transplant for this subgroup of highly sensitised patients. One of the objectives of the EUROSTAM project, (a Europe-wide Strategy to enhance Transplantation of highly sensitised patients on the basis of Acceptable HLA Mismatches) was to develop a tool to compare the chance of transplanting HSP in different European populations with donor organs from within and outside their own donor pool. Information on the HLA type and ABO blood group of the actual donor population, as well as the acceptable mismatches of long waiting HSP were obtained from the EUROSTAM partner organizations i.e. Eurotransplant (ET), UK National Health Service Blood and Transplant (NHSBT), Barcelona, Prague and Athens. Results from simulations using the newly developed tool shows that 195 (27%) of the 724 long waiting highly sensitised patients registered at each partner organisation have increased chances of transplant in a different European donor pool. This makes a strong case for sharing kidneys between European countries for selected difficult to transplant patients.

• MeSH
• Tissue Donors MeSH
• Histocompatibility MeSH
• HLA Antigens genetics   immunology   MeSH
• Immunization MeSH
• Humans MeSH
• Transplant Recipients MeSH
• Waiting Lists MeSH
• Histocompatibility Testing methods   MeSH
• Kidney Transplantation * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Editorial MeSH
• Geographicals
• Europe MeSH

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.

• MeSH
• Alleles MeSH
• B-Lymphocytes virology   MeSH
• Exons genetics   MeSH
• Genetic Variation MeSH
• Genetic Loci MeSH
• Genotype MeSH
• Haplotypes genetics   MeSH
• Histocompatibility MeSH
• HLA Antigens genetics   MeSH
• Homozygote MeSH
• Single-Blind Method MeSH
• Humans MeSH
• Histocompatibility Antigens Class I genetics   MeSH
• Histocompatibility Antigens Class II genetics   MeSH
• Sequence Analysis, DNA methods   MeSH
• Data Accuracy MeSH
• Histocompatibility Testing methods   MeSH
• Cell Line, Transformed MeSH
• Cell Transformation, Viral MeSH
• Herpesvirus 4, Human immunology   MeSH
• High-Throughput Nucleotide Sequencing methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories. Completion of the PT program with a minimum score of 95% concordance at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci satisfied the requirements to submit NGS HLA typing data for the 17th IHIW projects. Together, these PS and PT efforts constituted the 17th IHIW Quality Control project. Overall PT concordance rates for HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5 were 98.1%, 97.0% and 98.1%, 99.0%, 98.6%, 98.8%, 97.6%, 96.0%, 99.1%, 90.0% and 91.7%, respectively. Across all loci, the majority of the discordance was due to allele dropout. The high cost of NGS HLA genotyping per experiment likely prevented the retyping of initially failed HLA loci. Despite the high HLA genotype concordance rates of the software, there remains room for improvement in the assembly of more accurate consensus DNA sequences by NGS HLA genotyping software.

• MeSH
• Alleles MeSH
• Genotype * MeSH
• HLA Antigens genetics   MeSH
• Immunogenetics * MeSH
• Consensus Development Conferences as Topic MeSH
• Humans MeSH
• International Cooperation MeSH
• Pilot Projects MeSH
• Quality Control MeSH
• Software MeSH
• Histocompatibility Testing methods   MeSH
• High-Throughput Nucleotide Sequencing methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

A novel therapeutic approach to refractory acute antibody-mediated rejection (AMR) in kidney transplant recipients was applied in 23 patients based on administration of Bortezomib, intravenous corticosteroids, plasmapheresis and Rituximab. Application of Bortezomib regimen led to diminishing of donor-specific antibodies (DSA) to HLA-B (P = 0.004) and HLA-DR (P = 0.0005), but not to HLA-A (P = 0.106) and HLA-DQ antigens (P = 0.18). Patients with good clinical response to treatment had significantly better allograft survival than recipients with continuing deterioration of graft function (P = 0.019). Graft survival after therapy of refractory AMR was significantly worse than survival after first transplantation and was comparable with outcomes after retransplantation. In conclusion, therapy with Bortezomib was well tolerated and effective in decreasing the levels of HLA-B and -DR antibodies, however, was not successful in depleting HLA-A and -DQ DSA.

• MeSH
• Patient Safety MeSH
• Bortezomib therapeutic use   MeSH
• Tissue Donors MeSH
• Adult MeSH
• HLA Antigens genetics   immunology   MeSH
• Transplantation, Homologous MeSH
• Adrenal Cortex Hormones therapeutic use   MeSH
• Immunologic Factors therapeutic use   MeSH
• Isoantibodies blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Pilot Projects MeSH
• Plasmapheresis methods   MeSH
• Graft Survival * MeSH
• Prognosis MeSH
• Graft Rejection blood   diagnosis   immunology   pathology   MeSH
• Rituximab therapeutic use   MeSH
• Drug Administration Schedule MeSH
• Histocompatibility Testing methods   MeSH
• Kidney Transplantation * MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The aim of our study was to evaluate the relevance of complement-binding donor-specific antibodies (DSA) for prediction of antibody-mediated rejection (AMR) after liver transplantation. Sera from 123 liver transplant recipients were retrospectively defined for HLA specificity and complement-fixing activity using the single antigen beads, C1q and C3d techniques. Liver-recipients' sera were tested before transplantation, 3, 6 months and 1 year after transplantation. Patients were followed up for graft survival and rejection incidence for 1 year after transplantation. All patients with pretransplant complement-binding DSA developed severe AMR after transplantation, while three recipients out of four, who produced de novo complement-fixing DSA, developed AMR. Definition of DSA with respect to complement-fixing activity may provide clinically relevant information about the risk of AMR after liver transplantation.

• MeSH
• Tissue Donors MeSH
• Child MeSH
• Adult MeSH
• Transplantation, Homologous MeSH
• Isoantibodies blood   MeSH
• Complement C1q metabolism   MeSH
• Complement C3d metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Follow-Up Studies MeSH
• Graft Survival * MeSH
• Prognosis MeSH
• Graft Rejection blood   diagnosis   immunology   pathology   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Histocompatibility Testing methods   MeSH
• Liver Transplantation * MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: The selection of optimal donor is crucial for successful hematopoietic stem cell transplantation (HSCT). Thereby, it is appropriate to know, in addition to basic human leukocyte antigen (HLA) gene matches, other immunogenic or nonimmunogenic parameters predicting the outcome of transplant. OBJECTIVE: A unified approach is necessary to provide a comprehensive view of the patient-donor compatibility characterization outside of standard HLA genes. The approach should be applicable as a tool for optimizing procedures for extended donor typing and/or verification typing of a donor. METHODS: The study used the summary, unification, and innovation of existing practical knowledge and experience of the Czech National Marrow Donor Registry of various factors beyond HLA matching with impact on transplant outcome. RESULTS: An information technology system-implemented procedure (a verification algorithm) is presented as the decision support approach for prematurely discarding less suitable donors from the transplantation process. It is intended primarily for the transplant specialist to help establish optimal procedures for verifying and determining donor critical factors. CONCLUSIONS: A process defining HLAs, killer cell immunoglobulin-like receptors, and cytokine typing strategies was proposed to provide support to a transplant specialist in refining the choice of a suitable donor.

• MeSH
• Algorithms * MeSH
• HLA Antigens immunology   MeSH
• Humans MeSH
• Receptors, KIR immunology   MeSH
• Registries MeSH
• Decision Support Systems, Clinical * MeSH
• Histocompatibility Testing methods   MeSH
• Hematopoietic Stem Cell Transplantation methods   MeSH
• Donor Selection methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czechoslovakia MeSH

x

x

• MeSH
• Adaptive Immunity MeSH
• Allografts immunology   MeSH
• Antibody-Dependent Cell Cytotoxicity MeSH
• HLA Antigens immunology   MeSH
• Major Histocompatibility Complex MeSH
• Transplantation, Homologous MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Immunosuppression Therapy MeSH
• Humans MeSH
• Graft Survival immunology   MeSH
• Immunity, Innate MeSH
• Graft Rejection * diagnosis   immunology   prevention & control   MeSH
• Histocompatibility Testing methods   MeSH
• Organ Transplantation * MeSH
• Transplantation Tolerance * immunology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH