BACKGROUND: Sarcoidosis is an immune-mediated systemic disease with unknown etiology affecting the lung predominantly. The clinical manifestation of sarcoidosis is rather diverse ranging from Löfgren's syndrome to fibrotic disease. Also, it differs among patients with distinct geographical and ethnic origins, consistent with environmental and genetic factors' role in its pathogenesis. Of those, the polymorphic genes of the HLA system have been previously implicated in sarcoidosis. Therefore, we have performed an association study in a well-defined cohort of Czech patients aiming to define how variation in HLA genes, may contribute to disease origin and development. MATERIALS AND METHODS: Total of the 301 Czech unrelated sarcoidosis patients were diagnosed according to international guidelines. In those, HLA typing was performed using next-generation sequencing. The allele frequencies at six HLA loci (HLA-A,-B,-C,-DRB1,-DQA1, and -DQB1) observed in the patients were compared with HLA allele distribution determined in 309 unrelated healthy Czech subjects; sub-analyses of relationships between HLA and distinct sarcoidosis clinical phenotypes were performed. Associations were assessed by two-tailed Fischer's exact test with correction for multiple comparisons. RESULTS: We report two variants, HLA-DQB1*06:02, and HLA-DQB1*06:04, as risk factors for sarcoidosis, and three variants, HLA-DRB1*01:01, HLA-DQA1*03:01, and HLA-DQB1*03:02 as protective factors. HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, HLA-DQA1*05:01, and HLA-DQB1*02:01 variants associated with Löfgren's syndrome, a more benign phenotype. HLA- DRB1*03:01 and HLA-DQA1*05:01 alleles were connected with better prognosis-chest X-ray (CXR) stage 1, disease remission, and non-requirement of corticosteroid treatment. The alleles HLA-DRB1*11:01 and HLA-DQA1*05:05 are associated with more advanced disease represented by the CXR stages 2-4. HLA-DQB1*05:03 associated with sarcoidosis extrapulmonary manifestation. CONCLUSION: In our Czech cohort, we document some associations between sarcoidosis and HLA previously described in other populations. Further, we suggest novel susceptibility factors for sarcoidosis, such as HLA-DQB1*06:04, and characterize associations between HLA and sarcoidosis clinical phenotypes in Czech patients. Our study also extends the role of the 8.1 ancestral haplotype (HLA-A*01:01∼HLA-B*08:01∼HLA-C*07:01∼HLA-DRB1*03:01∼HLA-DQA1*05:01∼HLA-DQB1*02:01), already implicated in autoimmune diseases, as a possible predictor of better prognosis in sarcoidosis. The general translational application of our newly reported findings for personalized patient care should be validated by an independent study from another, international referral center.

• Publikační typ
• časopisecké články MeSH

Genetic susceptibility for sarcoidosis and Löfgren's syndrome (LS) has been associated with prognosis. Human leukocyte antigen (HLA)-DRB1*03 is over-represented in LS, and is associated with a good prognosis, whereas HLA-DRB1*15-positive patients have a more chronic course of sarcoidosis. These HLA-DRB1 types can be easily tagged by single nucleotide polymorphisms (SNPs). Our aim was to evaluate the association between these tag SNPs and bronchoalveolar lavage (BAL) characteristics. In 29 patients, both complete HLA-DRB1* locus genotyping and SNP tagging was performed in parallel. HLA-DRB1 type was inferred from the presence of *03 tag rs2040410 allele A and referred to as *03. HLA-DRB1*15 was inferred from the presence of tag SNP rs3135388 allele A and referred to as *15. For BAL analysis, 122 patients with LS and 165 patients with non-LS sarcoidosis were included. BAL lymphocyte subsets were analyzed by flow cytometry. The presence of tag SNPs completely corresponded with HLA-DRB1*03/*15 genotypes in all 29 patients in whom both HLA-DRB1* genotyping and SNP tagging was performed. In all patients together, *03+ /*15- patients showed a higher CD4+ /CD8+ ratio than *03- /*15+ (P = 0·004) and *03- /*15- (P = 0·001). LS patients with *03+ /*15- had a lower BAL lymphocyte count compared to *03- /*15+  patients (P = 0·011). Non-LS sarcoidosis patients with *03+ /*15- patients showed a decreased CD103+ CD4+ /CD4+ ratio compared to *03- /*15+  patients (P = 0·045) and *03- /*15- patients (P = 0·018). We found that HLA-DRB1*03 and HLA-DRB1*15 can be approximated by genotyping of tag SNPs and corresponds with the degree of lymphocytosis and cell phenotypes in BAL in both LS and non-LS sarcoidosis patients.

• MeSH
• alely * MeSH
• bronchoalveolární laváž MeSH
• CD4-pozitivní T-lymfocyty * imunologie   patologie   MeSH
• CD8-pozitivní T-lymfocyty * imunologie   patologie   MeSH
• dospělí MeSH
• genotypizační techniky MeSH
• HLA-DRB1 řetězec * genetika   imunologie   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní sarkoidóza * genetika   imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

After discovery of antiphospholipid syndrome (APS) our understanding of molecular mechanisms of living matter has become more sophisticated and on this way monocytes has become crucial player, particularly in pathogenesis of APS. Thrombotic and non-thrombotic complications of APS could be explained by monocytes' activation too. But mechanisms underlying their activation are poorly investigated. So we aimed to determine transcriptional activity of monocytes after exposing them to low concentrations of lipopolysaccharide (LPS) and LPS+ATP using comparative of RT-PCR. Our study included eleven women suffering from recurrent miscarriages and APS (mean age 30±5,6 years). Nine healthy women (mean age of 29±8,5 years) without a positive family history of APS, autoimmune diseases and thrombosis were chosen as a control group. The results showed increasing levels of TLR2, IL-23, CCL2, CXCL10, IL-1β and IL-6 in APS cells, while in healthy cells LPS resulted in IL-6 and STAT3 elevated mRNAs. Double stimulation of APS cells resulted in decreased mRNA levels of CCL-2, IL-1β, and mRNA NLRP3 in healthy cells. At the same time TLR2 mRNAs were elevated in both groups after double stimulation. Thus increased sensitivity of APS cells to LPS may contribute to thrombus formation. Low concentration of ATP diminishes LPS-induced inflammatory state of APS monocytes, which might be one of potential regulatory mechanisms.

• MeSH
• adenosintrifosfát farmakologie   MeSH
• antifosfolipidový syndrom imunologie   metabolismus   patologie   MeSH
• chemokiny krev   genetika   MeSH
• dospělí MeSH
• exprese genu MeSH
• habituální potrat imunologie   MeSH
• interleukiny krev   genetika   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• messenger RNA metabolismus   MeSH
• mladý dospělý MeSH
• monocyty účinky léků   imunologie   metabolismus   MeSH
• protein NLRP3 krev   genetika   MeSH
• studie případů a kontrol MeSH
• techniky in vitro MeSH
• toll-like receptor 2 krev   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Colchicine is an antimitotic drug which binds to tubulin and at high doses results in cytoskeleton disruption. Colchicine is believed to be an anti-inflammatory agent, though its modulatory effects on the level and transcriptional activity of genes is still a matter of debate. There is growing evidence that alterations in the cytoskeleton exert specific effects on the expression of various genes. This study was undertaken to analyze whether disrupting the microtubule cytoskeleton by colchicine modulates transcriptional levels of MEFV, NF-κB p65, NLRP3, HMGB1, and caspase-3 in neutrophils from patients with familial Mediterranean fever (FMF) and healthy subjects. In the present study, colchicine caused increased expression of NLRP3 (p=0.007) and MEFV (p=0.03), but had no effect on caspase-3, NF-κB p65 and HMGB1 genes in healthy neutrophils. FMF neutrophils were less responsive to the drug treatment. This study supports the hypothesis that, being an anti-inflammatory agent, colchicine at relatively high concentrations might lead to the activation of pro-inflammatory signalling pathways in neutrophils.

• MeSH
• cytoskeletální proteiny genetika   MeSH
• dospělí MeSH
• familiární středomořská horečka krev   farmakoterapie   genetika   MeSH
• kaspasa 3 genetika   MeSH
• kolchicin farmakologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neutrofily účinky léků   fyziologie   MeSH
• protein HMGB1 genetika   MeSH
• regulace genové exprese účinky léků   MeSH
• studie případů a kontrol MeSH
• transkripční faktor RelA genetika   MeSH
• transportní proteiny genetika   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

Colchicine (Col) is a microtubule depolymerizing drug, widely used for treatment of familial Mediterranean fever (FMF). Mechanisms by which Col exerts its beneficial effects are not yet completely understood, especially with respect to gene expression in polymorphonuclear neutrophils (PMNs), the main effector cells in acute inflammatory attacks of FMF. This study was, therefore, designed to elucidate possible modulatory effect of Col on expression of inflammation-related genes in circulating PMNs from 16 FMF patients in the remission period and 11 healthy subjects. In vitro effect of Col exposure (1 microg/ml) on expression of 8 selected genes was examined using quantitative real-time RT-PCR. Col up-regulated expression of IL-8 and IL-1beta genes in FMF (13-fold and 2.7-fold, p less than 0.05, respectively) and healthy (3-fold and 6.5-fold, p less than 0.05, respectively) PMNs, and down-regulated caspase-1 in FMF neutrophils (3-fold, p less than 0.05). In FMF PMNs treated with Col mRNAs of IL-8 (51-fold, p less than 0.01) and c-FOS (7-fold, p less than 0.05) transcripts were elevated compared to those from healthy subjects. By contrast, caspase-1 mRNA was decreased in FMF neutrophils compared to healthy cells (1.6-fold, p less than 0.05). Hereby, we provide evidence that, at least in vitro, Col displays pro-inflammatory potential in respect to IL-1beta and IL-8 genes. At the same time, our findings implicate suppression of caspase-1 expression by Col as a potential mechanism for its effects in FMF treatment.

• MeSH
• dospělí MeSH
• familiární středomořská horečka farmakoterapie   imunologie   MeSH
• interleukin-1beta genetika   MeSH
• interleukin-8 genetika   MeSH
• kaspasa 1 genetika   MeSH
• kolchicin farmakologie   terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• neutrofily účinky léků   metabolismus   MeSH
• regulace genové exprese účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

MicroRNAs (miRNAs) represent the most abundant class of regulators of gene expression in humans: they regulate one-third of human protein-coding genes. These small noncoding ∼22-nucleotides (nt)-long RNAs originate by multistep process from miRNA genes localized in the genomic DNA. To date, more than 1420 miRNAs have been identified in humans (miRBase v17). The main mechanism of miRNA action is the posttranscriptional regulation via RNA interference with their target mRNAs. The majority of target mRNAs (more than 80%) undergo degradation after recognition by complementary miRNA; the translational inhibition with little or no influence on mRNA levels has been also reported. Each miRNA may suppress multiple mRNA targets (average ∼200), and at the same time, one mRNA can be targeted by many miRNAs enabling to control a spectrum wide range of cellular processes. Recently, the role of miRNAs in the development of immune cells and the maintenance of immune system homeostasis gained attention, and the involvement of miRNAs in the pathogenesis of several immune system diseases has emerged. This review focuses on the role of miRNAs in autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis), inflammatory pathologies of distinct organ (atherosclerosis, osteoarthritis and atopic eczema) and/or systemic locations such as allergy. The role of miRNAs, their predicted and known mRNA targets and description of their actions in physiological immune reactions and in the pathological processes ongoing in immune-mediated human disorders will be discussed. Finally, miRNA-based diagnostics and therapeutic potentials will be highlighted.

• MeSH
• ateroskleróza genetika   imunologie   patologie   MeSH
• atopická dermatitida genetika   imunologie   patologie   MeSH
• epigeneze genetická imunologie   MeSH
• idiopatické střevní záněty genetika   imunologie   patologie   MeSH
• lidé MeSH
• messenger RNA genetika   imunologie   MeSH
• mikro RNA genetika   imunologie   MeSH
• osteoartróza genetika   imunologie   patologie   MeSH
• přirozená imunita MeSH
• psoriáza genetika   imunologie   patologie   MeSH
• revmatoidní artritida genetika   imunologie   patologie   MeSH
• RNA interference imunologie   MeSH
• roztroušená skleróza genetika   imunologie   patologie   MeSH
• stabilita RNA MeSH
• systémový lupus erythematodes genetika   imunologie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Since early 90', growing body of evidence indicates that the Mediterranean diet with mild to moderate consumption of wine, mostly red wine, has a protective effect on cardiovascular diseases. Several mechanisms have been discussed to participate in the beneficial effect of red wine, such as antioxidant or vasodilating activity. However, later it has been shown that also other alcoholic beverages have a protective effect on atherosclerosis. Up to now, data from the prospective, long-term, head-to-head comparisons of the effects of different drinks on markers of atherosclerosis are insufficient. METHODS: The IVV (in vino veritas) study is a long-term, prospective, multicenter, randomized trial comparing the effect of red and white wines on the markers of atherosclerosis. One hundred and twenty healthy subjects with mild to moderate risk of atherosclerosis will be randomized to regular consumption of red wine (Pinot Noir) or white wine (Chardonnay-Pinot) for one year. The primary endpoint is the level of HDL-cholesterol at one year, while secondary endpoints are levels of other markers of atherosclerosis (LDL-cholesterol, C-reactive protein, myeloperoxidase, advanced oxidation protein product, interleukins 6 and 18, matrix metalloproteinases, glutathione s-transferase, monocyte chemoattractant protein 1, soluble CD40L). CONCLUSION: The IVV trial is the first study focusing on the long-term prospective comparison of the effects of red and white wines consumption on HDL-cholesterol and other markers of atherosclerosis. Results of the IVV trial may extend our understanding of the widely discussed "French paradox" (Tab. 1, Ref. 21)

• MeSH
• ateroskleróza diagnóza   MeSH
• biologické markery krev   MeSH
• HDL-cholesterol MeSH
• lidé MeSH
• víno analýza   MeSH
• výzkumný projekt MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie 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

• MeSH
• alely MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• infarkt myokardu genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mozkový neurotrofický faktor genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• substituce aminokyselin genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH