Coeliac disease (CD) is an autoimmune disorder caused by the ingestion of gluten-containing grains. One of the prerequisites for the development of the disease is the presence of specific combinations of HLA alleles at the DQA1 and DQB1 loci. The HLA test is a supportive diagnostic test. In the Czech Republic, approximately 3,500 HLA tests for CD diagnosis are performed annually in almost three dozen laboratories. The HLA Department of the Institute of Haematology and Blood Transfusion in Prague has been offering the EPT "Detection of HLA Alleles Associated with Diseases" for more than 10 years. The results are evaluated in terms of the correct determination of predisposing alleles/allelic groups and clinical interpretation. Every year, we notice some problems with the detection of CD-associated alleles and the interpretation of results. Annual workshops are part of this EPT, and they also include recommendations for the interpretation of results. This interpretation is evolving based on the current knowledge in the field. The current recommendation for interpretation was adopted in 2023, dividing HLA-DQA1/DQB1 genotypes into three categories: 1) detected HLA genotype is associated with predisposition to coeliac disease; 2) coeliac disease could not be excluded based on the detected HLA genotype; 3) coeliac disease could be excluded with high probability based on the detected HLA genotype. The quality of examination is increasing but still needs improvement. Correct results and accurate interpretation can inform clinicians' decisions about the diagnosis of coeliac disease in appropriate patients.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Soft tissue sarcomas are aggressive mesenchymal-origin malignancies. Undifferentiated pleomorphic sarcoma (UPS) belongs to the aggressive, high-grade, and least characterized sarcoma subtype, affecting multiple tissues and metastasizing to many organs. The treatment of localized UPS includes surgery in combination with radiation therapy. Metastatic forms are treated with chemotherapy. Immunotherapy is a promising treatment modality for many cancers. However, the development of immunotherapy for UPS is limited due to its heterogeneity, antigenic landscape variation, lower infiltration with immune cells, and a limited number of established patient-derived UPS cell lines for preclinical research. In this study, we established and characterized a novel patient-derived UPS cell line, JBT19. The JBT19 cells express PD-L1 and collagen, a ligand of the immune checkpoint molecule LAIR-1. JBT19 cells can form spheroids in vitro and solid tumors in immunodeficient nude mice. We found JBT19 cells induce expansion of JBT19-reactive autologous and allogeneic NK, T, and NKT-like cells, and the reactivity of the expanded cells was associated with cytotoxic impact on JBT19 cells. The PD-1 and LAIR-1 ligand-expressing JBT19 cells show ex vivo immunogenicity and effective in vivo xenoengraftment properties that can offer a unique resource in the preclinical research developing novel immunotherapeutic interventions in the treatment of UPS.

• MeSH
• antigeny CD274 metabolismus   MeSH
• buněčné linie MeSH
• imunoterapie MeSH
• lidé MeSH
• ligandy MeSH
• maligní fibrózní histiocytom * MeSH
• myši nahé MeSH
• myši MeSH
• sarkom * patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

HLA-A*29:172 allele differs from HLA-A*29:01:01:01 by one missense single C/G nucleotide exchange in codon 77.

• MeSH
• alely MeSH
• exony genetika   MeSH
• exprese genu MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• sekvenční seřazení MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Nucleophosmin (NPM1, B23) is a multifunctional phosphoprotein expressed in all tissues. The protein is mainly localized in nucleoli. In hematological malignancies, NPM1 belongs to commonly altered genes. Its mutation, always heterozygous, leads to the re-localization of the NPM1 protein from the nucleolus to the cytoplasm (NPM1c+). NPM1c+ is found in 30% of acute myeloid leukemia (AML). Our study showed that an AML patient, whose leukemia cells carried the NPM1c+ mutation and who was the recipient of allogeneic HSCT from a haploidentical donor, raised a robust allorestricted CD8+ T cell response directed against the NPM1wt protein. Favourably, the response against NPM1wt was not accompanied by side effects such as GvHD. Moreover, the induction of a high NPM1wt-specific response coincided with the decrease in NPM1c+ transcripts detected, implying a beneficial graft versus leukemia effect. On the basis of these results, we suppose that TCRs from allorestricted NPM1wt-specific T cells are worth studying in other recipients of grafts from haploidentical donors as a possible tool for TCR gene therapy.

• MeSH
• akutní myeloidní leukemie * genetika   metabolismus   terapie   MeSH
• CD8-pozitivní T-lymfocyty metabolismus   patologie   MeSH
• hematopoetické kmenové buňky metabolismus   patologie   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• nukleofosmin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: This work summarizes our experience with WT1 monitoring before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: The expression of WT1 gene was measured by real-time polymerase chain reaction in peripheral blood according to the European Leukemia Net recommendations. Between May 2005 and August 2019, we analyzed 147 consecutive patients with acute myeloid leukemia with high WT1 expression at diagnosis, transplanted in first (CR1) or second (CR2) complete remission. RESULTS: At the time of allo-HSCT, 107 patients had WT1-normal expression (WT1 ≤ 50 copies), and 40 patients had WT1-high expression. The median follow-up was 21 months. The estimated 5-year overall survival and event-free survival was significantly better in the WT1-normal cohort (65% and 57% vs. 37% and 25%; P = .0003 and P < .0001, respectively) and 5-year cumulative incidence of relapse was significantly lower in the WT1-normal group (19% vs. 53%; P < .0001). Five-year non-relapse mortality was not significantly different (20% and 23%). Multivariate analysis revealed WT1-high expression and acute graft-versus-host disease grade 3/4 as significantly negative prognostic factors for OS. Overall, 49 patients developed WT1 molecular relapse in the post-transplant period; in 14 cases, the therapeutic intervention was done. In all but 1 relapsed patient where WT1 minimal residual disease (MRD) was monitored (38 patients), we detected WT1-high levels (sensitivity of 97%). CONCLUSION: The results of the analysis confirmed our previous experience that WT1 status before allo-HSCT is a strong prognostic factor for both OS and relapse risk. In addition, we confirmed the usefulness of this marker for MRD monitoring after allo-HSCT. The main advantage is the possibility of frequent MRD monitoring in peripheral blood and early bone marrow examination based on WT1-high expression.

• MeSH
• akutní myeloidní leukemie krev   genetika   mortalita   terapie   MeSH
• dospělí MeSH
• hodnocení rizik metody   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru epidemiologie   genetika   MeSH
• mladý dospělý MeSH
• nádorové biomarkery krev   metabolismus   MeSH
• následné studie MeSH
• nemoc štěpu proti hostiteli diagnóza   epidemiologie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• proteiny WT1 krev   metabolismus   MeSH
• regulace genové exprese u leukemie MeSH
• reziduální nádor MeSH
• rizikové faktory MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• studie proveditelnosti MeSH
• stupeň závažnosti nemoci MeSH
• transplantace hematopoetických kmenových buněk škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Předmětem naší práce je analýza vlivu imunologických parametrů s cílem optimalizace rutinního výběru nepříbuzných dárců krvetvorných buněk. Základním požadavkem úspěšnosti transplantace je shoda mezi dárcem a příjemcem v HLA systému I. a II. třídy. Využití genetických metod pro určení shody v HLA I. třídy znamenalo v našem souboru zlepšení přežití transplantovaných pacientů. Další zpřesnění genetických metod ale již žádné významné zlepšení nepřineslo. U souboru 240 dárců byla sledována míra shody v HLA-DPB1, pouze 8,2 % z nich bylo shodných se svými pacienty. Dalších 114 dárců mělo neshody tolerovatelné dle klinického prognostického modelu DPB1 T-Cell Epitope Algorithm. Netolerovatelné neshody byly detekovány u 37 % dárců. KIR genotyp, který ovlivňuje potransplantační průběh především u pacientů s akutní myeloidní leukemií (AML), byl testován u 347 dárců, 70 % bylo zařazeno do kategorie „neutrální“, 19,3 % bylo v kategorii „lepší“ a 10, 7 % v kategorii „nejlepší“ dle Donor KIR B-content group calculator. Zastoupení jednotlivých kategorií se nelišilo mezi skupinou neselektovaných dárců a dárců vybraných pro transplantaci pro pacienty s AML. Do rutinního výběru dárců bylo zařazeno vyhledání dle tolerovatelnosti neshod v HLA-DPB1, kategorie KIR jsou pouze doplňkovým parametrem aktuálního algoritmu výběru dárců.

The aim of our work was to analyse the influence of immunological parameters in order to optimize routine selection of unrelated stem cell donors. Match in HLA class I and II between the donor and the recipient is the essential requirement for success of the transplantation. The use of genetic methods for match determination in HLA class I improved survival of transplanted patients in our cohort. Further refinement of genetic methods has not resulted in any significant improvement. In a group of 240 donors, the match rate in HLA-DPB1 was monitored, only 8.2% were comletely matched with their patients. Another 114 donors had mismatches tolerable in the DPB1 T-Cell Epitope Algorithm clinical prognostic model. Intolerable mismatches were detected in 37% of donors. The KIR genotype, which affects the post-transplantation course especially in patients with acute myeloid leukemia (AML), was tested in 347 donors, 70% were classified as “neutral”, 19.3% were in “better” and 10.7% in “best” category by Donor KIR B-content group calculator. The representation of individual categories did not differ between the group of non-selected donors and donors selected for transplantation for patients with AML. Routine selection of donors included a search according to the tolerability of mismatches in HLA-DPB1, KIR categories are only a supplementary parameter of the current donor selection algorithm.

• MeSH
• HLA antigeny genetika   imunologie   MeSH
• lidé MeSH
• nepříbuzný dárce MeSH
• prospektivní studie MeSH
• receptory KIR genetika   imunologie   MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• výběr dárců * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH