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.

• 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

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

Prosthetic joint infection (PJI) is a serious complication of the total joint arthroplasty (TJA). Serum mannose-binding lectin (MBL), a pattern recognition receptor, is involved in antibacterial immune response. This study investigated whether functional variants of the MBL2 gene may be associated with the risk of PJI. MBL2 -550 (H/L, rs11003125), MBL2 -221 (Y/X, rs7096206) and MBL2 +54 (G/A, rs1800450) single nucleotide polymorphisms (SNP) were genotyped in 112 PJI patients and two control groups: 245 patients with aseptic TJA and 196 Czech population controls without TJA. Serum MBL concentration was assessed in PJI patients (n = 92) and aseptic TJA controls (n = 56). The distribution of MBL2 genotypes complied with the Hardy-Weinberg equilibrium in all investigated groups. Importantly, MBL2 -550 L allele (allelic frequency, 0.72) and LL genotype (genotype frequency, 0.51) were more frequent among PJI patients compared to aseptic TJA controls (L allele: 0.63, P = 0.016, P(c) = 0.048; LL genotype: 0.39, P = 0.037, P(c) > 0.05) and to Czech population controls (L allele: 0.61, P = 0.010, P(c) = 0.030; LL genotype: 0.35, P = 0.006, P(c) = 0.018), respectively. Regarding MBL protein, the MBL2 -550 L carriers presented with lower serum MBL concentrations than non-carriers (median; 593 vs 1876 ng/ml; P < 0.01). Similarly, the carriage of MBL2 -221 X and 54 A alleles was associated with lower serum MBL concentrations (P < 0.01). In conclusion, MBL2 -550 genetic variant(s) associated with low serum concentration of MBL protein can increase the risk of PJI.

• MeSH
• alely MeSH
• artroplastika škodlivé účinky   MeSH
• běloši MeSH
• dospělí MeSH
• frekvence genu MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• klouby metabolismus   patologie   chirurgie   MeSH
• lektin vázající mannosu krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osteoartróza krev   genetika   chirurgie   MeSH
• riziko MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zánět etiologie   genetika   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Despite the independent segregation of genes encoding killer immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA), there is some evidence of some kind of co-evolution. Therefore, one could expect reduced KIR diversity within the HLA restricted population. A total of 41 unrelated individuals homozygous for ancestral HLA haplotype AH8.1 (HLA-A*0101-Cw*0701-B*0801-DRB1*0301-DQB1*0201) were genotyped for KIRs. Over all, 14 different genotypes were identified. The KIR genes and genotypes repertoire generally mirror the published frequencies in Caucasians. Except for KIR2DS4, all activating genes presented frequencies below 50%. KIR2DS5 was the least frequent among activating genes (17%), whereas KIR2DL5 (37%) among inhibitory ones. The most frequent (39%) was AA genotype. Twenty-two individuals (54%) had a copy of KIR haplotypes A and B (AB genotype), whereas three (7%) were homozygous for B (BB genotype). Nine of fourteen reported genotypes occurred only in one individual. Five genotypes were reported in less than twenty individuals worldwide and one genotype was reported so far only once. Conversely, the three most frequent genotypes account for 68% of all detected genotypes. The results show the unrestricted KIR diversity in this HLA uniform group and support the fact that the driving force for KIR evolution is not exclusively a major histocompatibility complex.

• MeSH
• DNA analýza   genetika   MeSH
• frekvence genu MeSH
• genotyp MeSH
• haplotypy genetika   MeSH
• HLA antigeny genetika   MeSH
• homozygot MeSH
• lidé MeSH
• polymerázová řetězová reakce MeSH
• populační skupiny genetika   MeSH
• receptory KIR genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Recent unconfirmed literature data suggest that elevated concentrations of the multifunctional cytokine hepatocyte growth factor (HGF) might be a marker of increased incidence of acute rejection after organ transplantation. The aim of this study was to test the hypothesis that HGF levels may correlate with the rejection and/or with the production of HLA and MHC Class I chain-related antigens A (MICA) specific antibodies. Sixty-three heart transplant recipients were included into the study. Hundred and eighty-five endomyocardial biopsies (EMB) obtained up to 6 months after transplantation were retrospectively analyzed for signs of cellular (CR) and antibody-mediated rejection (AMR). Pre- and post-transplant sera were tested for HGF concentrations and antibodies to HLA class I, class II and MICA antigens by xMap technology (Luminex). Pre-transplant HGF did not correlate with the incidence of CR or AMR. However, higher HGF concentrations correlated significantly with HLA antibody production before and after transplantation (P = 0.006 and P < 0.0001 respectively). Patients with both HLA class I and class II antibodies before transplantation had significantly lower AMR-free survival. Furthermore, recipients with pre-transplant donor-specific antibodies (DSA) had significantly lower AMR-free survival (50%) than recipients without pre-transplant HLA antibodies (90%) and patients with antibodies not specific to donor antigens (92%) (P = 0.005). Post-transplant MICA antibodies tended to be more frequent in patients with AMR (P = 0.063). In conclusion, elevated HGF concentrations in our study were not associated with the incidence of CR and/or AMR but with the presence of HLA-specific antibodies. Testing for DSA before heart transplantation by Luminex may be helpful for the identification of patients with increased risk of AMR.

• MeSH
• akutní nemoc MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• hepatocytární růstový faktor krev   MeSH
• histokompatibilita - antigeny třídy I imunologie   MeSH
• HLA antigeny imunologie   MeSH
• isoprotilátky krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• rejekce štěpu diagnóza   etiologie   imunologie   MeSH
• retrospektivní studie MeSH
• transplantace srdce škodlivé účinky   imunologie   patologie   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

Idiopathic pulmonary fibrosis (IPF), a severe lung disease with unknown aetiology, is thought to have an important genetic component. Single nucleotide polymorphism, C5507G, of the complement receptor 1 (CR1) gene, which affects the number of CR1 molecules on erythrocytes, has been associated with susceptibility to IPF in a single European population. To replicate this finding, 53 Czech IPF patients with 203 Czech healthy control subjects and 70 English IPF patients with 149 English controls were investigated. In both populations, there were no significant differences in distribution of CR1 C5507G variants between IPF patients and their appropriate control groups. In conclusion, the association of the CR1 C5507G polymorphism with susceptibility to IPF was not reproducible in Czech and English populations.

• MeSH
• alely MeSH
• běloši genetika   MeSH
• dospělí MeSH
• financování organizované MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní fibróza epidemiologie   genetika   MeSH
• polymorfismus genetický MeSH
• receptory komplementu 3b genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response. The frequencies of the variants profoundly differ among populations and so does the associated risk. We examined the associations of variants in the CARD15, TNFA and PTPN22 genes with pediatric-onset and adult-onset CD in the Czech population. Genotype, phenotype and allelic frequencies were compared between 345 patients with CD (136 pediatric-onset and 209 adult-onset patients) and 501 unrelated healthy controls. At least one minor allele of the CARD15 gene was carried by 46% patients and only 21% control subjects (OR = 3.2, 95% CI 2.4-4.4). In a multiple logistic regression model, the strongest association with CD was found for the 1007fs variant (OR = 4.6, 95% CI 3.0-7.0), followed by p.G908R (OR = 2.9, 95% CI 1.5-5.7) and p.R702W (OR = 1.7, 95% CI 1.0-2.9), while no independent association was found for the remaining variants in the CARD15 gene (p.268S, p.955I and p.289S), for the p.R620W variant in the PTPN22 gene or for the g.-308G>A variant in the TNFA gene. The age at CD onset was strongly modified by positivity for the 1007fs allele: it was present in 42% pediatric-onset and only 25% adult-onset patients. In conclusion, we report a high frequency of the minor allele of the CARD15 1007fs polymorphism in the Czech population and a strong effect of this allele on the age at disease onset.

• MeSH
• Crohnova nemoc genetika   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• financování organizované MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• mladiství MeSH
• signální adaptorový protein Nod2 genetika   imunologie   MeSH
• studie případů a kontrol MeSH
• TNF-alfa genetika   imunologie   MeSH
• tyrosinfosfatasa nereceptorového typu 22 genetika   imunologie   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH
• Geografické názvy
• Česká republika MeSH

The expression of CD27 and CD44 correlate with the genotype of B-precursor acute lymphoblastic leukemia (ALL). Based on the expression of these antigens, we identified counterparts of TEL/AML1(pos) and TEL/AML1(neg) leukemic cells in nonmalignant bone marrow. Although CD27 is known as a marker of mature memory B cells, we recently showed that CD27 is also expressed by malignant and nonmalignant B precursors. Here, we show that CD27 and CD44 delineate stages of B-precursor development. Well-established differentiation markers showed that the developmental sequence starts from undetermined progenitors, expressing CD44. Upon B-lineage commitment, cells gain CD27 and lose CD44. The CD27(pos)CD44(neg) (CD27 single positive, 27SP) cells are the earliest stage within CD10(pos)CD19(pos) B precursors and express RAG-1 and TDT. These cells correspond to TEL/AML1(pos) ALL (1/4 pediatric B-precursor ALL). The development follows to CD27/CD44 double-positive (27/44DP) stage, 44SP stage and CD27/CD44 double-negative (27/44DN) stage. Before exit to periphery, CD44 is reexpressed. The 27/44DP cells are mostly large and profoundly suppress RAG-1. Despite their presumably high proliferation potential, 27/44DP cells rarely dominate in leukemia. At 44SP stage, which corresponds to TEL/AML1(neg) leukemias, RAG-1 is reexpressed and Ig light chain gene starts to be rearranged.

• MeSH
• antigeny CD27 biosyntéza   fyziologie   genetika   MeSH
• antigeny CD44 biosyntéza   fyziologie   genetika   MeSH
• dítě MeSH
• financování organizované MeSH
• genová přestavba B-lymfocytů imunologie   MeSH
• imunofenotypizace MeSH
• leukemie B-buněčná diagnóza   genetika   imunologie   MeSH
• lidé MeSH
• lymfopoéza genetika   imunologie   MeSH
• prekurzorové B-lymfoidní buňky cytologie   imunologie   patologie   MeSH
• vývojová regulace genové exprese MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH

A single nucleotide polymorphism (SNP) C5507G of the complement receptor 1 (CR1) gene has been associated with genetic susceptibility to sarcoidosis in an Italian population. In order to provide further data on the possible involvement of CR1 gene polymorphisms in sarcoidosis, CR1 SNPs C5507G and A3650G were investigated in Czech (n = 210) and Dutch (n = 116) patients with sarcoidosis with ethnically matched groups of healthy control subjects (Czech, n = 203; Dutch, n = 112). CR1 C5507G and A3650G SNPs were not associated with susceptibility to sarcoidosis or its clinical course. Further, CR1 messenger RNA expression in bronchoalveolar lavage cells investigated by quantitative reverse transcriptase-polymerase chain reaction did not differ between sarcoidosis patients and control subjects and was not associated with the presence of the CR1 5507*G allele.

• MeSH
• dospělí MeSH
• financování organizované MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• plicní sarkoidóza genetika   MeSH
• receptory komplementu 3b genetika   MeSH
• sarkoidóza genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH
• Nizozemsko MeSH

Identification of a novel HLA-DRB1*1458 allele within a Caucasian individual using sequence-based typing.

• MeSH
• alely MeSH
• dospělí MeSH
• HLA-DR antigeny MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• sekvence nukleotidů MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• Geografické názvy
• Česká republika MeSH