The ELISpot assay is a sensitive technique applied to assess cytokine-producing memory/effector T cells and human leukocyte antigens (HLA)-specific IgG-producing B cells. Besides the fact that the method is laborious and is difficult to standardise between laboratories, it may provide valuable information on the immune response of recipients before and after organ transplantation. In this article, we briefly review the recent literature and discuss the clinical significance of the ELISpot assay in predicting the risk and incidence of allograft rejection and survival.

• Klíčová slova
• ELISpot, HLA, antibodies, interferon-gamma, organ transplantation, rejection,
• MeSH
• ELISPOT MeSH
• interferon gama MeSH
• lidé MeSH
• rejekce štěpu * MeSH
• T-lymfocyty MeSH
• transplantace ledvin * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• interferon gama MeSH

Loss of heterozygosity is considered to be the most common type of tumour-specific somatic mutation of the human leucocyte antigens (HLA) genes in patients with haematological malignancies. Nevertheless, subtle DNA sequence changes, namely short insertions/deletions, may also abolish the expression of HLA molecules and interfere with routine HLA typing. Two male patients with acute myelogenous leukaemia (AML) were indicated for the search of a suitable donor for allogeneic haematopoietic stem cell transplantation (aHSCT). The patients and their relatives were initially HLA typed by serological and DNA techniques at a low-resolution level. The HLA high-resolution (HR) type was obtained by means of sequencing-based typing (SBT). In both cases, anomalous frameshifts in the sequence were observed in the HLA-B gene, namely in exon 3 (Case 1, heterozygous deletion of two bases) and exon 4 (Case 2, heterozygous insertion of two bases). In the second case, the insertion variant was associated with a loss of HLA-B8 expression. To reveal whether these sequence patterns may be caused by somatic mutations in the malignant cells, blood sample in remission (Case 1) and buccal swab sample (Case 2) were collected from the patients. In an important manner, the SBT in these germline samples revealed common HLA-B*07:02,*15:01 (Case 1) and HLA-B*08:01,*35:02 (Case 2) types with no evidence for the sequence alteration observed in the initial samples. In conclusion, the insertion/deletion sequence variants of the HLA-B gene in two patients were limited to the initial blood samples with a substantial proportion of AML cells and thus may be attributed to the somatic mutation in the malignant cells. HLA somatic mutations should be taken into account in patients with haematological malignancies to prevent HLA mistyping and inappropriate selection of an aHSCT donor.

• Klíčová slova
• HLA, allograft/allogeneic transplantation, cancer - leukaemia/haematologic, immune response,
• MeSH
• akutní myeloidní leukemie genetika   MeSH
• HLA-B7 antigen genetika   MeSH
• HLA-B8 antigen genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace INDEL * MeSH
• nádorové proteiny genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• HLA-B*07:02 antigen MeSH Prohlížeč
• HLA-B*08:01 antigen MeSH Prohlížeč
• HLA-B7 antigen MeSH
• HLA-B8 antigen MeSH
• nádorové proteiny MeSH

Haematopoietic stem cell transplantation (HSCT) remains the only cure for most haematological malignancies, however, the mortality rate remains high. Complications after HSCT include relapse, graft versus host disease (GvHD), graft rejection and infection. Over the last few years several groups, have demonstrated that non-HLA gene polymorphisms can be predictive of outcome after HSCT. Since the glucocorticoid cortisol is pivotal in the regulation of the immune system, we decided to examine single nucleotide polymorphisms (SNPs; rs6198, rs33388 and rs33389) within the glucocorticoid receptor (GR) and correlate with HSCT outcome. The training set consisted of patients (n = 458) who underwent HSCT for acute leukaemia between 1983 and 2005. In the recipients, the absence of the ACT haplotype and absence of the T allele of rs33388 were associated with decreased OS and the absence of the ACT haplotype, the absence of the T allele of rs33388 and the presence of the ATA haplotype were associated with increased risk of relapse. In addition, the presence of the ACT haplotype in the recipient showed a trend to be associated with increased risk of chronic graft versus host disease (cGvHD). The patients in this cohort received mainly myeloablative conditioning (n = 327). The SNPs in the glucocorticoid receptor were then investigated in a validation set (n = 251) of HSCT patients transplanted for acute leukaemia from 2006. This cohort contained significantly more patients that had received reduced intensity conditioning (RIC). Some of the results could be validated in these patients. However, contrary to the training set, the absence of the haplotype ACT in the donor in this cohort was associated with increased risk of cGvHD. Differences in the conditioning were shown to influence the results. These results are the first to associate GR SNPs with HSCT outcome and demonstrate the inherent problems of replicating SNP association studies in HSCT, due to different pre-transplant regimens.

• Klíčová slova
• chronic graft versus host disease, haplotype, inflammation aGVHD, polymorphisms, relapse,
• Publikační typ
• časopisecké články MeSH

Differential expression of HLA-DQA1 and HLA-DQB1 gene alleles was analysed in three different cell populations isolated from peripheral blood-B lymphocytes, monocytes and whole-blood cells. Interallelic differences in mRNA levels were observed: DQA1*03 alleles were among the most expressed in all cell types, whereas DQA1*05 alleles were least expressed in whole blood and monocytes and among the most expressed in B cells. For DQB1 gene, DQB1*06 group of alleles were the most expressed, and DQB1*02 group the least expressed within all cell populations examined. In comparison with the rest alleles, DQB1*06 and DQB1*05:02 alleles have higher expression in monocytes than in B cells, professional antigen-presenting cells. Cell type-specific regulation of expression was observed as well, with higher and more balanced expression of alleles in B lymphocytes compared to monocytes.

• Klíčová slova
• HLA class II, HLA-DQA1, HLA-DQB1, antigen presentation, gene expression, genetic polymorphism,
• MeSH
• alely MeSH
• B-lymfocyty imunologie   metabolismus   MeSH
• dospělí MeSH
• exprese genu * MeSH
• frekvence genu MeSH
• haplotypy MeSH
• HLA-DQ alfa řetězec genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• mladý dospělý MeSH
• monocyty imunologie   metabolismus   MeSH
• orgánová specificita MeSH
• senioři MeSH
• zdraví dobrovolníci pro lékařské studie 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
• Názvy látek
• HLA-DQ alfa řetězec MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQA1 antigen MeSH Prohlížeč
• HLA-DQB1 antigen MeSH Prohlížeč
• messenger RNA MeSH

The EBMT risk score is an established tool successfully used in the prognosis of survival post-HSCT and is applicable for a range of haematological disorders. One of its main advantages is that score generation involves summation of clinical parameters that are available pretransplant. However, the EBMT risk score is recognized as not being optimal. Previous analyses, involving patients with various diagnoses, have shown that non-HLA gene polymorphisms influence outcome after allogeneic HSCT. This study is novel as it focuses only on patients having acute leukaemia (N = 458) and attempts to demonstrate how non-HLA gene polymorphisms can be added to the EBMT risk score in a Cox regression model to improve prognostic ability for overall survival. The results of the study found that three genetic factors improved EBMT risk score. The presence of MAL (rs8177374) allele T in the patient, absence of glucocorticoid receptor haplotype (consisting of rs6198, rs33389 and rs33388) ACT in the patient and absence of heat-shock protein 70-hom (+2437) (rs2227956) allele C in the patient were associated with decreased survival time. When compared to the EBMT risk score, the scores combining EBMT risk score with the genetic factors had an improved correlation with clinical outcome and better separation of risk groups. A bootstrapping technique, involving repeated testing of a model using multiple validation sets, also revealed that the newly proposed model had improved predictive value when compared to the EBMT risk score alone. Results support the view that non-HLA polymorphisms could be useful for pretransplant clinical assessment and provide evidence that polymorphisms in the recipient genotype may influence incoming donor cells, suppressing the initiation of the graft versus leukaemia effect and reducing survival.

• MeSH
• dospělí MeSH
• genomika MeSH
• genotyp MeSH
• haplotypy genetika   MeSH
• homologní transplantace škodlivé účinky   MeSH
• leukemie genetika   imunologie   patologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoc štěpu proti hostiteli imunologie   MeSH
• prognóza MeSH
• proteiny tepelného šoku HSP70 genetika   MeSH
• rizikové faktory MeSH
• testování histokompatibility MeSH
• transplantace hematopoetických kmenových buněk škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny tepelného šoku HSP70 MeSH

The identification of a novel HLA-B*35:279 allele in a Czech patient is described. This allele is identical to the B*35:03:01 variant except the G/A nucleotide exchange at position 652 of the HLA-B gene that corresponds to the amino acid substitution from valine to isoleucine in alpha 3 domain of the HLA-B antigen.

• MeSH
• alely * MeSH
• HLA-B antigeny genetika   imunologie   izolace a purifikace   MeSH
• lidé MeSH
• sekvence nukleotidů MeSH
• substituce aminokyselin MeSH
• testování histokompatibility MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• HLA-B antigeny MeSH

The two-nucleotide deletion recently detected in the mannose-binding lectin 2 gene in purebred and crossbred domestic pigs was not found among 68 wild boars representing 4 populations from Europe and Asia. This suggests that the deletion is a result of breeding and/or genetic drift/bottle necks.

• MeSH
• frekvence genu MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus MeSH
• lektin vázající mannosu genetika   MeSH
• molekulární sekvence - údaje MeSH
• mutace INDEL MeSH
• sekvenční delece MeSH
• Sus scrofa genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Japonsko MeSH
• Rakousko MeSH
• Švédsko MeSH
• Názvy látek
• lektin vázající mannosu MeSH

We describe the identification of a novel HLA-DRB1 allele, DRB1*13:116, in a member of the Czech National Marrow Donor Registry. The novel allele differs from the known DRB1*13:17 variant by a nucleotide exchange at position 227 (T/A) of the coding HLA-DRB1 sequence, which causes an amino acid substitution (Phe47Tyr) in the HLA-DR beta 1 chain.

• MeSH
• alely MeSH
• dárci tkání MeSH
• dospělí MeSH
• HLA-DRB1 řetězec genetika   MeSH
• kostní dřeň imunologie   fyziologie   MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• registrace MeSH
• sekvence nukleotidů MeSH
• substituce aminokyselin MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HLA-DRB1 řetězec MeSH

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL-6, IL-13 and IL-15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti-CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL-6, IL-13 and IL-15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL-15 -267C/T polymorphism. A higher prevalence of heterozygote variants of IL-15 polymorphisms (14035A/T and -267C/T) in the RF IgG- and RF IgA-negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL-15 with circulating level of IL-15 (14035A/T and 367G/A) and with total RF and Ig-specific RFs (-267C/T) was found. The relation of IL-15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL-13 polymorphism -1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL-15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL-15 levels in circulation to RFs.

• MeSH
• alely MeSH
• autoprotilátky krev   MeSH
• dospělí MeSH
• genetické asociační studie MeSH
• haplotypy MeSH
• imunoglobulin A krev   imunologie   MeSH
• imunoglobulin G krev   imunologie   MeSH
• imunoglobulin M krev   imunologie   MeSH
• interleukin-13 genetika   MeSH
• interleukin-15 genetika   MeSH
• interleukin-6 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• progrese nemoci MeSH
• revmatoidní artritida krev   genetika   MeSH
• revmatoidní faktor krev   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
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• imunoglobulin A MeSH
• imunoglobulin G MeSH
• imunoglobulin M MeSH
• interleukin-13 MeSH
• interleukin-15 MeSH
• interleukin-6 MeSH
• revmatoidní faktor MeSH

The single nucleotide polymorphism (SNP) G949T in the mannose-binding lectin ( MBL ) 1 gene has been associated with low MBL-A concentration in serum and detected at different frequencies in various European pig populations. However, the origin of this SNP is not known. Part of the MBL1 gene was sequenced in 12 wild boar/Large White crossbred pigs from the second backcross (BC 2 ) generation in a family material originating from two wild boar x Large White intercrosses. Also, MBL-A serum concentration was measured in the entire BC 2 generation (n = 45). Furthermore, the genotypes of 68 wild boars from Sweden, Austria, the Czech Republic, and Japan were determined in regard to five previously described SNPs in MBL1 . The T allele of G949T was present among the BC 2 animals. MBL-A serum concentration in the BC 2 animals showed a bimodal distribution, with one-third of the animals at levels between 0.7 and 1.6 μg mL(-1) and the remaining pigs at levels around 13 μg mL(-1) . There was a co-variation between the presence of the T allele and low MBL-A concentration in serum. The genotyping of the wild boars revealed differences between populations. The T allele of G949T was not detected in the Austrian and Japanese samples and is thus unlikely to be an original feature of wild boars. In contrast, it was present at high frequency (0.35) among the Swedish wild boars, probably representing a founder effect. Five MBL1 haplotypes were resolved. Only two of these were present among the Japanese wild boars compared to four in each of the European populations. This difference may reflect differences in selection pressure and population history.

• MeSH
• frekvence genu MeSH
• genotyp MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus MeSH
• lektin vázající mannosu krev   genetika   MeSH
• receptory rozpoznávající vzory genetika   MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA veterinární   MeSH
• Sus scrofa genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Japonsko MeSH
• Rakousko MeSH
• Švédsko MeSH
• Názvy látek
• lektin vázající mannosu MeSH
• receptory rozpoznávající vzory MeSH