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.

• Klíčová slova
• CWD catalogues, HLA allele frequencies, HLA biostatistical tools, HLA databases, HLA population genetics, HLA workshops,
• 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
• Názvy látek
• HLA antigeny * MeSH

The guidelines for the implementation and reporting of HLA nomenclature for the World Marrow Donor Association have served as a reliable standard for communication of HLA data in the hematopoietic cell transplantation process. Wider use of next-generation sequencing made a special provision of the guidelines increasingly pertinent: how to communicate novel HLA alleles. Novel alleles need to be recognized by the WHO Nomenclature Committee for Factors of the HLA system to obtain official allele designations. Until then they have to be handled according to the specific rules. Leaving the actual rules basically unchanged we give some advice on how to communicate novel alleles to best facilitate the search process for cases where novel alleles are identified on donor or patient side.

• Klíčová slova
• HLA, NGS typing, donor registry, new alleles, patient registry,
• MeSH
• alely MeSH
• HLA antigeny genetika   MeSH
• kostní dřeň * MeSH
• lidé MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• HLA antigeny 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.

• Klíčová slova
• HLA, allogeneic transplantation, new alleles, polymorphism, typing,
• 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
• Názvy látek
• HLA-A29 antigen MeSH Prohlížeč

A somatic mutation of the human leukocyte antigen (HLA)-A gene revealed in tumour cells of acute myelogenous leukemia (AML) is described. A patient with AML and her siblings were routinely typed for HLA in order to find a suitable donor for haematopoietic stem cell transplantation. Sequencing-based typing of the initial patient's sample characterized by high proportion of blasts revealed unknown G/A exchange at position 781 of the HLA-A gene (exon 4) associated with HLA-A*02:01 allele. Importantly, this G781A variant was completely absent in the patient's remission sample obtained after the clearance of blasts. Our results are a reminder that HLA mutations in tumour cells may interfere with routine HLA typing and should always be considered, namely, in patients with haematological malignancies.

• Klíčová slova
• human leukocyte antigen typing, major histocompatibility complex, new HLA allele, polymorphism, somatic mutation,
• MeSH
• akutní myeloidní leukemie genetika   patologie   terapie   MeSH
• alely MeSH
• bodová mutace * MeSH
• dospělí MeSH
• exony genetika   MeSH
• HLA-A2 antigen genetika   MeSH
• indukce remise MeSH
• lidé MeSH
• missense mutace * MeSH
• molekulární sekvence - údaje MeSH
• nádorové kmenové buňky chemie   MeSH
• sekvence nukleotidů MeSH
• sourozenci MeSH
• substituce aminokyselin MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HLA-A*02:01 antigen MeSH Prohlížeč
• HLA-A2 antigen 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
• Názvy látek
• HLA-A*02 antigen MeSH Prohlížeč
• HLA-A2 antigen MeSH
• nesmyslný kodon MeSH
• terminační kodon MeSH

HLA-A*2418 is described for the first time. It segregates in a Mendelian fashion. Serological analyses indicate that the new allele encodes epitopes from both HLA-A9 and -A3 specificities. Results from nucleotide sequencing analyses of polymerase chain reaction (PCR) amplification products derived from genomic and cDNA are compatible with those findings.

• MeSH
• alely * MeSH
• HLA-A antigeny genetika   MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• HLA-A antigeny 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 Holotype™ kit and HLATwin software™. 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
• histokompatibilita - antigeny třídy I genetika   MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé MeSH
• sarkoidóza * genetika   MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histokompatibilita - antigeny třídy I MeSH
• HLA-DRB1 řetězec MeSH

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10-5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10-53 and HLA-DRB1*03:01, p=3.25×10-9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10-26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10-11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10-13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10-6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10-64) and position 9 of HLA-B (p=7.03×10-11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.

• Klíčová slova
• HLA, autoantibody, genetics, idiopathic inflammatory myopathy, myositis,
• MeSH
• alely MeSH
• autoprotilátky genetika   imunologie   MeSH
• běloši genetika   MeSH
• dospělí MeSH
• genotyp MeSH
• haplotypy MeSH
• HLA-DRB1 řetězec genetika   imunologie   MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida genetika   imunologie   MeSH
• polymorfismus genetický MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• HLA-DRB1 řetězec MeSH

Currently, 10 different amino acid variants of the HLA-DRB1*12 family are known. We here report the identification of a new HLA-DRB1*12 allele in a healthy Caucasian male individual. The allele was detected by sequencing-based typing during confirmatory high-resolution typing of an unrelated, male, potential donor from the Czech National Marrow Donors Registry. Compared with DRB1*120101, to which it is closest, the new variant is characterized by a new replacement mutation (T-->C) at nucleotide position 126 of exon 2, resulting in the amino acid substitution Phe-->Leu at position 47. Computational analysis reveals that position 47 functions as a keystone in the beta(1) domain, joining both segments of the alpha helix with the beta sheet, and plays a major role in the structural conformation of the binding groove. Additionally, position 47 is part of pocket E of the peptide binding groove and is directly involved in peptide binding. The new allele, DRB1*1211, is therefore likely to differ substantially from other DRB1*12 alleles in its peptide binding repertoire and alloreactive potential.

• MeSH
• běloši MeSH
• bodová mutace * MeSH
• HLA-DR antigeny chemie   genetika   imunologie   MeSH
• HLA-DRB1 řetězec MeSH
• konformace proteinů MeSH
• krystalografie rentgenová MeSH
• lidé středního věku MeSH
• lidé MeSH
• substituce aminokyselin MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HLA-DR antigeny MeSH
• HLA-DRB1 řetězec MeSH

STUDY OBJECTIVES: To identify rare allelic variants and HLA alleles in narcolepsy patients with hypocretin (orexin, HCRT) deficiency but lacking DQB1*06:02. SETTINGS: China (Peking University People's Hospital), Czech Republic (Charles University), Denmark (Golstrup Hospital), Italy (University of Bologna), Korea (Catholic University), and USA (Stanford University). DESIGN: CSF hypocretin-1, DQB1*06:02, clinical and polysomnographic data were collected in narcolepsy patients (552 with and 144 without cataplexy) from 6 sites. Numbers of cases with and without DQB1*06:02 and low CSF hypocretin-1 were compiled. HLA class I (A, B, C), class II (DRBs, DQA1, DQB1, DPA1, and DPB1), and whole exome sequencing were conducted in 9 DQB1*06:02 negative cases with low CSF hypocretin-1. Sanger sequencing of selected exons in DNMT1, HCRT, and MOG was performed to exclude mutations in known narcolepsy-associated genes. MEASUREMENTS AND RESULTS: Classic narcolepsy markers DQB1*06:02 and low CSF hypocretin-1 were found in 87.4% of cases with cataplexy, and in 20.0% without cataplexy. Nine cases (all with cataplexy) were DQB1*06:02 negative with low CSF hypocretin-1, constituting 1.7% [0.8%-3.4%] of all cases with cataplexy and 1.8% [0.8%-3.4%] of cases with low CSF hypocretin independent of cataplexy across sites. Five HLA negative subjects had severe cataplexy, often occurring without clear triggers. Subjects had diverse ethnic backgrounds and HLA alleles at all loci, suggesting no single secondary HLA association. The rare subtype DPB1*0901, and homologous DPB1*10:01 subtype, were present in 5 subjects, suggesting a secondary association with HLA-DP. Preprohypocretin sequencing revealed no mutations beyond one previously reported in a very early onset case. No new MOG or DNMT1 mutations were found, nor were suspicious or private variants in novel genes identified through exome sequencing. CONCLUSIONS: Hypocretin, MOG, or DNMT1 mutations are exceptional findings in DQB1*06:02 negative cases with hypocretin deficiency. A secondary HLA-DP association may be present in these cases. These represent particularly difficult diagnostic challenges.

• Klíčová slova
• DNMT1, HLA, MHC, MOG, cataplexy, exome sequencing, hypocretin, narcolepsy, orexin,
• MeSH
• alely MeSH
• glykoprotein v myelinu oligodendrocytů genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• internacionalita MeSH
• intracelulární signální peptidy a proteiny mozkomíšní mok   nedostatek   genetika   MeSH
• kataplexie genetika   MeSH
• kohortové studie MeSH
• lidé MeSH
• mutace genetika   MeSH
• mutační analýza DNA MeSH
• narkolepsie genetika   MeSH
• neuropeptidy mozkomíšní mok   nedostatek   genetika   MeSH
• orexiny MeSH
• represorové proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DMAP1 protein, human MeSH Prohlížeč
• glykoprotein v myelinu oligodendrocytů MeSH
• HCRT protein, human MeSH Prohlížeč
• HLA-DQ beta řetězec MeSH
• HLA-DQB1 antigen MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• MOG protein, human MeSH Prohlížeč
• neuropeptidy MeSH
• orexiny MeSH
• represorové proteiny MeSH