A comprehensive knowledge of human leukocyte antigen (HLA) molecular variation worldwide is essential in human population genetics research and disease association studies and is also indispensable for clinical applications such as allogeneic hematopoietic cell transplantation, where ensuring HLA compatibility between donors and recipients is paramount. Enormous progress has been made in this field thanks to several decades of HLA population studies allowing the development of helpful databases and bioinformatics tools. However, it is still difficult to appraise the global HLA population diversity in a synthetic way. We thus introduce here a novel approach, based on approximately 2000 data sets, to assess this complexity by providing a fundamental synopsis of the most frequent HLA alleles observed in different regions of the world. This new knowledge will be useful not only as a fundamental reference for basic research, but also as an efficient guide for clinicians working in the field of transplantation.

• MeSH
• alely * MeSH
• frekvence genu MeSH
• HLA antigeny * genetika   imunologie   MeSH
• lidé MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Analyzovali jsme frekvenci HLA alel ve třech skupinách autoimunitních endokrinopatií: A. skupina 30 pacientů s autoimunitní tyreoiditidou, B. skupina 20 pacientů s polyglandulární aktivací autoimunity, C. skupina 10 pacientů s autoimunitním polyglandulárním syndromem II. typu. Skupiny byly definovány na základě klinického obrazu a serologických parametrů. Jako kontrola sloužila americká databáze výskytu HLA u zdravých dárců krve kavkazské populace. Ve skupině A jsme nalezli statisticky významně vyšší výskyt HLA-A24 (21,7%) v porovnání se skupinou B (5,0%) a s kontrolami (8,5%) a HLA-B27 (15,0%) a HLA-DR11 (20%) v porovnání s kontrolami (4,2%, 8,5% ). Ve skupině B jsme nalezli statisticky významně vyšší výskyt HLA-A3 (25,0%) v porovnání se skupinou A (10%) a s kontrolami (11,8%) a HLA-B8 (22,5%) v porovnání se skupinou A (8,3%) a s kontrolami (8,6%). Ve skupině C jsme nalezli statisticky významně vyšší výskyt HLA-DR3 (30,0%) v porovnání se skupinou A (10,0%) a s kontrolami (9,8%) a HLA-B8 (30,0%) v porovnání se skupinou A (8,3%) a s kontrolami (8,6%). Genetické markery ukazují na podobnost skupin B a C. Může se jednat o vývojová stadia, ale přesto nás některé odlišnosti vedou k úvaze, zda odlišný epigenetický vliv nemůže prohloubit rozdíl mezi těmito skupinami v klinickém vývoji.

We analyzed the frequencies of HLA alleles in three groups of patients with autoimmune endocrinopathies: A. group of 30 patients with autoimmune thyroiditis, B. group of 20 patients with polyglandular activation of autoimmunity, C. group of 10 patients with autoimmune polyglandular syndrome type II. The groups were defined by clinical symptoms and by serological parameters. As controls served US database of the frequencies of HLA antigens in healthy blood donors of Caucasian population. We found statistically significantly higher occurrence of HLA-A24 in group A (21.7%) as compared with group B (5.0%), and with controls (8.5%), of HLA-A3 in group B (25.0%) as compared with group A (10%), and with controls (11.8%), of HLA-B8 in group B (22.5%) as compared with group A (8.3%), and with controls (8.6%), and in group C (30.0%) as compared with group A (8.3%) and with controls (8.6%), of HLA-B27 in group A (15.0%) as compared with controls (4.2%), of HLA-DR3 in group C (30.0%) as compared with group A (10.0%) and with controls (9.8%), of HLA-DR11 in group A (20%) as compared with controls (8.5%). Genetic markers show the similarity of the groups B and C. They can represent different stages of the same disease, but still some differences lead us to the idea, whether different epigenetic factors could not stress the difference between these groups in the clinical development.

• MeSH
• autoimunita MeSH
• autoimunitní nemoci MeSH
• autoimunitní tyreoiditida MeSH
• autoprotilátky analýza   MeSH
• ELISA MeSH
• finanční podpora výzkumu jako téma MeSH
• HLA antigeny analýza   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH

• MeSH
• alely MeSH
• HLA antigeny genetika   MeSH
• sekvence aminokyselin genetika   MeSH
• vazba proteinů genetika   MeSH
• Publikační typ
• příručky MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• NLK Obory
• genetika, lékařská genetika
• alergologie a imunologie

One hundred and eighty Czech individuals from the Czech Republic pop 3 were genotyped at the HLA-DRB1, -DQA1 and -DQB1 loci using sequence-specific primers PCR methods. HLA-DRB1, -DQA1 and -DQB1 genotypes are consistent with expected Hardy-Weinberg (HW) proportions. These genotype data are available in the Allele Frequencies Net Database under identifier AFND.

• MeSH
• alely MeSH
• frekvence genu MeSH
• genotyp * MeSH
• haplotypy MeSH
• HLA-DQ alfa řetězec genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé MeSH
• populační genetika * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

The new HLA-A*02:395N allele differs from A*02:01:01 at one nucleotide position in the exon 2.

• MeSH
• alely * MeSH
• dárci tkání MeSH
• databáze genetické MeSH
• exony genetika   MeSH
• HLA-A2 antigen genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nesmyslný kodon genetika   MeSH
• terminační kodon genetika   MeSH
• testování histokompatibility MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Polymorphic genes with immune functions, namely those of the human leukocyte antigen (HLA) system, have been implicated in sarcoidosis pathogenesis. As HLA polymorphisms in sarcoidosis have not been yet investigated in the Korean population, we used next-generation sequencing (NGS), allowing detailed characterization of HLA alleles to investigate the role of HLA variation in Korean sarcoidosis patients. We enrolled 103 patients diagnosed by the ATS/ERS/WASOG guidelines at Asan Medical Centre, Seoul, Korea. Among those, genotyping of 7 HLA loci (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -DPB1) was performed using Omixon HolotypeTM kit and HLATwin softwareTM. HLA allele frequencies were compared with frequency data on healthy Koreans from the allelic frequency databases, and 4-digit characteristics of HLA genotyping were used. Associations were assessed by two-tailed Fischer's exact test with correction for multiple comparisons. Variants previously associated with sarcoidosis risk (HLA-C*03:04, HLA-DRB1*12:01, HLA-DRB1*14:54) and a known protective variant HLA-DPB1*04:01, were associated with sarcoidosis in Koreans. Further, we suggest new HLA variants associated with sarcoidosis risk (e.g., HLA-DQA1*05:08) and novel protective variants HLA-DQB1*03:02 and HLA-DQA1*01:02 in Koreans. This first study of HLA variation in Korean patients with sarcoidosis by precise genotyping methodology reports data that could serve future meta-analyses on HLA variation's role in sarcoidosis.

• MeSH
• alely MeSH
• frekvence genu MeSH
• haplotypy MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé MeSH
• MHC antigeny I. třídy genetika   MeSH
• sarkoidóza * genetika   MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A, -B, -C) and class-II (HLA-DRB1, -DQA1, -DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length, -DQB1 from intron 1 to 3' UTR, and -DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening.

• MeSH
• běloši genetika   MeSH
• dárci krve MeSH
• dospělí MeSH
• frekvence genu MeSH
• haplotypy MeSH
• HLA-A antigeny genetika   MeSH
• HLA-B antigeny genetika   MeSH
• HLA-C antigeny genetika   MeSH
• HLA-DQ alfa řetězec genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• sekvenční analýza DNA MeSH
• vazebná nerovnováha MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Chorvatsko 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
• alely MeSH
• B-lymfocyty virologie   MeSH
• exony genetika   MeSH
• genetická variace MeSH
• genetické lokusy MeSH
• genotyp MeSH
• haplotypy genetika   MeSH
• histokompatibilita MeSH
• HLA antigeny genetika   MeSH
• homozygot MeSH
• jednoduchá slepá metoda MeSH
• lidé MeSH
• MHC antigeny I. třídy genetika   MeSH
• MHC antigeny II. třídy genetika   MeSH
• sekvenční analýza DNA metody   MeSH
• správnost dat MeSH
• testování histokompatibility metody   MeSH
• transformované buněčné linie MeSH
• virová transformace buněk MeSH
• virus Epsteinův-Barrové imunologie   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Peptides eluted from peripheral blood cells of HLA-B*2705 healthy donor were analyzed by LC MALDI MS/MS and LC ESI FTMS techniques. The sequences of 92 peptide ligands identified from one healthy blood donor by LC MALDI-TOF MS/MS were compared with those previously published from in vitro long-term cell cultures available in SYFPEITHI database and splenocytes. It was found that 18 sequences confirmed within 1ppm mass error by LC ESI FTMS were already described and 3 of them matched with those previously reported from HLA-B*2705 splenocytes. Another 38 sequences validated within the same mass error were not found in SYFPEITHI database and are identified here for the first time. Finally, 36 sequences (5 sequences already published in SYFPEITHI database) were evaluated by LC MALDI-TOF MS/MS but no matches in the list of monoisotopic masses obtained from LC ESI FTMS were found.

• MeSH
• alkoholoxidoreduktasy MeSH
• ankylózující spondylitida genetika   metabolismus   MeSH
• autoimunita genetika   MeSH
• databáze proteinů MeSH
• dospělí MeSH
• endopeptidasy metabolismus   MeSH
• financování organizované MeSH
• genetická predispozice k nemoci MeSH
• histony genetika   metabolismus   MeSH
• HLA-B27 antigen analýza   imunologie   izolace a purifikace   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• interakční proteinové domény a motivy MeSH
• krevní buňky imunologie   metabolismus   MeSH
• lidé MeSH
• peptidové mapování MeSH
• peptidy analýza   imunologie   izolace a purifikace   MeSH
• proteiny tepelného šoku HSC70 genetika   imunologie   krev   MeSH
• proteiny vázající GTP - alfa-podjednotky Gs genetika   imunologie   krev   MeSH
• sekvenční seřazení MeSH
• software MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH

Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute myeloid leukemia (AML) and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal individuals (large datasets available from Allele Frequency Net Database). Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B(*)07, B(*)18, and B(*)40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein.

• MeSH
• akutní myeloidní leukemie imunologie   MeSH
• analýza přežití MeSH
• imunita * MeSH
• jaderné proteiny chemie   genetika   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• MHC antigeny I. třídy imunologie   MeSH
• molekulární sekvence - údaje MeSH
• mutace genetika   MeSH
• mutantní proteiny chemie   metabolismus   MeSH
• peptidy chemie   imunologie   MeSH
• sekvence aminokyselin MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH