To investigate the disturbance in serum levels of interleukin-17 (IL-17) and transforming growth factor-beta1 (TGF-β1) and gene expression of retinoic acid-related orphan receptor-gamma t (ROR-γt) and forkhead box-P3 (FOX-P3) in patients with systemic lupus erythematosus (SLE) and to study their association with disease pathogenicity and activity. Newly diagnosed active patients with SLE (n=88) and healthy volunteers (n=70) were included. Serum IL-17 and TGF-β1 were measured using enzyme-linked immunosorbent assay. Gene-expression profiles of ROR-γt and FOX-P3 were screened using real-time polymerase chain reaction. The IL-17/TGF-β1 and ROR-γt/FOX-P3 levels were also calculated. The mean age of the patients was 30.96±8.25 years; they were 82 women and 6 men. Of the patients, 11.4% manifested mild disease while 88.6% had severe disease. The serum level of TGF-β1 was significantly lower (70.2±34.9 vs. 200.23±124.77 pg/ml), while both IL-17 (614.7±317.5 vs. 279.76±110.65 pg/ml) and IL-17/TGF-β1 (18.5±30.1 vs. 1.66±0.9) levels were significantly higher, in patients than in controls (p<0.0001). The gene-expression level of FOX-P3 (0.6±0.8 vs. 13.68±39.35) was reported to be lower, while ROR-γt (3.9±3.5 vs. 1.99±2.09) and ROR-γt/FOX-P3 (18.6±21.1 vs. 7.63±17.19) levels were significantly higher, in patients than in controls (p<0.0001). Disturbance in serum levels of IL-17 and TGF-β1 in T helper-17 and T-regulatory cells proliferation was highlighted through an imbalance in the gene expression of FOX-P3 and ROR-γt, as both are signature genes for the two cell types, respectively. These findings underscore the critical role of IL-17 and TGF-β1 in SLE development, rendering them potential targets for developing novel immunotherapeutic strategies.

• MeSH
• dospělí MeSH
• eozinofilní kationtový protein MeSH
• exprese genu MeSH
• forkhead transkripční faktory metabolismus   MeSH
• interleukin-17 genetika   MeSH
• jaderné receptory - podrodina 1, skupina F, člen 3 genetika   MeSH
• lidé MeSH
• mladý dospělý MeSH
• systémový lupus erythematodes * genetika   metabolismus   MeSH
• transformující růstový faktor beta1 * genetika   MeSH
• tretinoin MeSH
• virulence MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study aims to investigate the associations of hypomethylation and over expression of the TLR9 gene with systemic lupus erythematosus (SLE). Fifteen SLE patients who were diagnosed and not treated, were selected as cases, and 32 healthy subjects were enrolled as controls. DNA and total RNA of peripheral blood mononuclear cells (PBMCs) were extracted. The methylation status of the promoter region CpG motifs of the TLR9 gene was quantitatively measured using bisulfite sequencing PCR, and the mRNA expression of the TLR9 gene was determined using real-time fluorescent quantitative PCR. The methylation level of the 10 TLR9 CpG motifs of gene did not show difference between cases and controls (P>0.05). By contrast, we observed an abnormal increase of TLT9 mRNA expression in patients (P=9.379×10(-8)), which was significantly correlated with SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) (P=9.018×10(-7)). The change of TLR9 gene expression may play an important role in the pathogenesis of SLE.

• MeSH
• dospělí MeSH
• exprese genu MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA biosyntéza   genetika   MeSH
• metylace DNA fyziologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• polymerázová řetězová reakce metody   MeSH
• progrese nemoci * MeSH
• systémový lupus erythematodes krev   diagnóza   genetika   MeSH
• toll-like receptor 9 biosyntéza   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Overactivation of the innate immune system together with the impaired downstream pathway of type I interferon-responding genes is a hallmark of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To date, limited data on the cross-disease innate gene signature exists among those diseases. We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood mononuclear cells from well-defined patients with active stages of RA (n = 36, DAS28 ≥ 3.2), SLE (n = 28, SLEDAI > 6), and SSc (n = 22, revised EUSTAR index > 2.25). Emerging diversity and abundance of the innate signature in RA patients were detected: RA was characterized by the upregulation of TLR3, TLR5, IL1RAP/IL1R3, IL18R1, and SIGIRR/IL1R8 when compared to SSc (Pcorr < 0.02) and of TLR2, TLR5, and SIGIRR/IL1R8 when compared to SLE (Pcorr < 0.02). Applying the association rule analysis, six rules (combinations and expression of genes describing disease) were identified for RA (most frequently included high TLR3 and/or IL1RAP/IL1R3) and three rules for SLE (low IL1RN and IL18R1) and SSc (low TLR5 and IL18R1). This first cross-disease study identified emerging heterogeneity in the innate signature of RA patients with many upregulated innate genes compared to that of SLE and SSc.

• MeSH
• dospělí MeSH
• interleukin-1 genetika   metabolismus   MeSH
• interleukin-8 genetika   metabolismus   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• přirozená imunita genetika   MeSH
• receptory interleukinu-1 - typ I genetika   metabolismus   MeSH
• revmatoidní artritida krev   genetika   imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• systémová sklerodermie krev   genetika   imunologie   MeSH
• systémový lupus erythematodes krev   genetika   imunologie   MeSH
• toll-like receptory genetika   metabolismus   MeSH
• transkriptom MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• ankylózující spondylitida epidemiologie   genetika   MeSH
• autoimunitní nemoci genetika   imunologie   MeSH
• diagnostické techniky molekulární MeSH
• dna (nemoc) epidemiologie   genetika   MeSH
• dnavá artritida epidemiologie   genetika   MeSH
• genetická predispozice k nemoci epidemiologie   genetika   MeSH
• hyperurikemie epidemiologie   genetika   metabolismus   MeSH
• incidence MeSH
• lidé MeSH
• psoriatická artritida epidemiologie   genetika   MeSH
• revmatické nemoci * genetika   imunologie   MeSH
• revmatoidní artritida epidemiologie   genetika   MeSH
• systémový lupus erythematodes epidemiologie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVES: To analyse the expression regulation of two inducible HSP70 genes - HSPA1A and HSPA1B - located within the major histocompatibility complex (MHC) in patients with various systemic autoimmune diseases and to prove the reliability of MHC-located HSP70 genes as molecular markers reflecting the autoimmune process. METHODS: 94 adult patients with idiopathic inflammatory myopathy (IIM, n=31), systemic lupus erythematosus (SLE, n=31) or systemic sclerosis (SSc, n=32) and 37 healthy individuals were analysed. The mRNA expression level was determined using quantitative real-time PCR method. The expression of intracellular HSP70 was established by flow cytometry, the extracellular HSP70 protein was measured in plasma samples using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of HSPA1A gene was significantly up-regulated in patients with autoimmune diseases (SLE: p<0.01; SSc: p<0.01; IIM: p<0.0001) compared to healthy controls. The expression of HSPA1B gene was increased only in patients with myositis (p<0.05). Furthermore, the HSPA1B gene expression is associated with the HLA-DRB1*03 risk allele in patients with IIM. In addition, we have found a relation between HSPA1A gene expression regulation and the presence of disease specific autoantibodies in patients with SLE and myositis. The level of intracellular HSP70 was not increased; however, the level of extracellular HSP70 protein was increased in patients suffering from SSc and IIM as compared to controls. CONCLUSIONS: The results suggest an involvement of the MHC-linked HSP70 genes in the pathology of studied autoimmune disorders. Therefore, the HSPA1A and HSPA1B genes might serve as an interesting candidate molecule for development of distinct types of autoimmunities.

• MeSH
• alely MeSH
• autoimunita genetika   MeSH
• autoprotilátky MeSH
• biologické markery MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida genetika   imunologie   MeSH
• proteiny tepelného šoku HSP70 genetika   MeSH
• regulace genové exprese MeSH
• senioři MeSH
• systémová sklerodermie genetika   imunologie   MeSH
• systémový lupus erythematodes genetika   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• imunopatogeneze, netóza,
• MeSH
• apoptóza imunologie   MeSH
• biologická terapie MeSH
• dermatomyozitida imunologie   komplikace   patofyziologie   MeSH
• extracelulární matrix imunologie   patologie   MeSH
• lidé MeSH
• pojivová tkáň * imunologie   patofyziologie   MeSH
• polymyozitida imunologie   komplikace   patofyziologie   MeSH
• revmatoidní artritida diagnóza   farmakoterapie   genetika   imunologie   patofyziologie   terapie   MeSH
• ribonukleoproteiny analýza   imunologie   MeSH
• smíšené onemocnění pojiva imunologie   patofyziologie   MeSH
• systémová sklerodermie etiologie   imunologie   patofyziologie   patologie   MeSH
• systémový lupus erythematodes diagnóza   genetika   imunologie   patofyziologie   terapie   MeSH
• zánět * imunologie   klasifikace   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Small non-coding RNA molecules (miRs) are involved in immune cell maturation and function and might influence immunopathological processes of systemic lupus erythematosus (SLE) pathogenesis. METHODS AND RESULTS: This paper presents the results of a literature search for publications dealing with the relationship between miRs and pathological factors related to SLE such as genetic background, immune dysregulation and gender-associated differences participating in SLE development. In SLE, distinct miRs are differentially expressed in SLE cells of innate and adaptive immunity. The miR-146a and miR-155 genes, among others, interfere with intracellular signalling pathways downstream of toll-like receptors 7 and 9 (TLR- 7, TLR-9) and influences interferon (IFN)-type I synthesis in plasmacytoid dendritic cells. In T and B cells, miR-126, miR-21, miR-146a, miR-155, miR-1246 and others might influence gene expression by epigenetic modifications, support abnormal cytosine release, differentiation of cell subsets, B cell hyperactivity and autoantibody production. Besides, estrogen might up- and downregulate immunologically active miRs, which are potential mediators of hormonal influences in SLE development. Moreover, SLE genetic basis included some polymorphisms of the miR-146a gene, which varies across populations. CONCLUSION: Distinct miRs are differentially expressed in both SLE mice models and human patients and promote autoimmune features of immune processes. MiRs are important molecules modulating susceptibility to SLE as well as its onset, clinical diversity and progression.

• MeSH
• adaptivní imunita fyziologie   MeSH
• B-lymfocyty imunologie   MeSH
• estrogeny fyziologie   MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• mikro RNA genetika   fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• přirozená imunita fyziologie   MeSH
• systémový lupus erythematodes etiologie   genetika   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. Moreover, anti-BAFF therapy seems to be a promising approach in treatment of B-cell derived leukemias/lymphomas. In nonhematologic solid tumors, BAFF may contribute to cancer progression by mechanisms both dependent on and independent of BAFF's proinflammatory role. We also describe ongoing research into the pathophysiological link between BAFF and cancer-related cachexia. BAFF has been shown to contribute to inflammation and insulin resistance which are known to worsen cancer cachexia syndrome. Taking all the above together, BAFF is emerging as a biomarker of several malignancies and a possible hallmark of cancer cachexia.

• MeSH
• B-lymfocyty metabolismus   patologie   MeSH
• faktor aktivující B-buňky genetika   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• kachexie genetika   patologie   MeSH
• lidé MeSH
• mnohočetný myelom genetika   patologie   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• nádorové biomarkery genetika   MeSH
• systémový lupus erythematodes farmakoterapie   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy 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

Úvod: V multifaktoriální etiopatogenezi systémových revmatických chorob je nezbytná genetická vnímavost. PRL je účinný imunomodulátor, který podporuje rozvoj autoimunity. Cíle práce: 1. Zjistit imunogenetický background, HLA II. a I. třídy a alely mikrosatelitového polymorfismu transmembránové části exonu 5 genu MIC-A (dále MIC-A), u SLE a PsA. 2. Zjistit, zda PRL v séru a synoviální tekutině ovlivňuje klinický a laboratorní průběh RA. 3. Zjistit, zda se funkční polymorfismus -1149 G/T SNP mimohypofyzárního promotoru PRL genu podílí na rozvoji a fenotypu SLE, RA, PsA, SSc a zánětlivých myopatií. Metodika: Genetické analýzy u souborů nemocných se SLE (n = 156), RA (n = 173), PsA (n = 100), SSc (n = 75), PM (n = 47) a DM (n = 68) a 123 zdravých jedinců: PCR-SSP (HLA I. a II. třídy), PCR-fragmentační analýza (MIC-A) a PCR-RFLP (-1149 G/T SNP PRL). Detekce PRL v séru a synoviální tekutině u 29 RA a 26 OA pomocí radioimunometrické analýzy. Výsledky: 1. Rizikové imunogenetické markery SLE v české populaci jsou alela HLA-DRB1*03 (pc = 0,008; OR 2,5) a haplotyp HLA-DRB1 *03-DQB1*0201 (pc <0,001; OR 4,54). Frekvence MIC-A5.1 je vyšší u SLE než u zdravých (pc =0,005; OR 1,88). MIC-A5.1 spolu s HLA-DRB1*03 výrazně zvyšuje riziko SLE, pc <0,000001; OR 9,71. Alela HLA-Cw*0602 je častější u PsA s psoriázou I. typu než u zdravých, pc <0,05; OR 3,33, 2. V séru i synoviální tekutině jsou hladiny PRL vyšší u RA (299,55 ± 27,28 a 338,85 ± 33,49 mIU/l) než u OA, 230,59 ± 16,61 a 245,97 ± 21,88 mIU/l, obě p<0,05. Hladiny synoviálního PRL korelují s DAS-28, p=0,010 a sérový PRL s tíží rentgenového postižení, p=0,014. 3. GT genotyp -1149 G/T SNP PRL se vyskytuje signifikantně častěji u nemocných s RA než u zdravých jedinců, pc =0,039; OR 1,82. Genotyp GG je signifikantně častější u SLE se začátkem choroby mezi 21.-40. rokem v porovnání s ostatními, pc =0,023; OR 2,94. Obdobně je genotyp TT vzácný u SSc nemocných se začátkem choroby po 45. roce (4,1 %) na rozdíl od nemocných se začátkem před 45. rokem (25 %), pc = 0,02; OR 0,13. Závěr: Tato práce je první imunogenetickou studií u dvou závažných revmatických chorob, SLE a PsA, v české populaci. Zjistili jsme, že alela MIC-A5.1 výrazně zvyšuje riziko SLE u HLA-DRB1*03 pozitivních osob. U PsA s psoriázou I. typu jsme potvrdili rizikovou alelu HLA-Cw*0602. PRL ovlivňuje průběh systémových revmatických onemocnění - u RA reflektuje aktivitu a tíží onemocnění, distribuce genotypů -1149 G/T SNP PRL se liší kvůli závislosti na věku objevení se SLE a SSc.

Background: Several factors like genetic susceptibility are required for the development of systemic rheumatic diseases. Prolactin (PRL) is an effective immunomodulator which supports the development of autoimmunity. Objectives: 1. To detect the immunogenetic background (HLA class I and II alleles and alleles of microsatellite polymorphism of the transmembrane part exon 5 of MIC-A gene (MIC-A)) in SLE and PsA.2. To detect PRL levels in serum and synovial fluid with regard to clinical and laboratory activity of RA. 3. To examine the role of the functional polymorphism -1149G/T SNP of extrapituitary promoter of PRL gene in the development and phenotype of SLE, RA, PsA, SSc and inflammatory myopathies. Methods: Genetic analyses were performed in patients with SLE (n=156), RA (n=173), PsA (n=100), SSc (n=75), PM (n=47), DM (n=68) and 123 healthy individuals using PCR-SSP (HLA class I and II), PCR-fragment analysis (MIC-A) and PCR-RFLP (-1149 G/T SNP PRL). In 29 RA and 26 OA PRL serum and synovial fluid concentrations were detected using immunoradiometric assay. Results: 1. The allele HLA-DRB1*03 (pc=0.008; OR 2.5) and haplotype HLA-DRB1*03- DQB1*0201 (pc <0.001; OR 4.54) were determined as risk immunogenetic markers for SLE in the Czech population. The allele MIC-A5.1 was increased in SLE compared to controls (pc =0.005; OR 1.88). MIC-A5.1 together with HLA-DRB1*03 significantly increases the risk for the development of SLE, pc <0.000001; OR 9.71. The alexprelele HLA-Cw*0602 occurs more frequently in PsA with psoriasis type I compared to controls, pc <0.05; OR 3.33. 2. Serum and synovial fluid PRL levels were increased in RA (299.55Ī27.28 and 338.85Ī 33.49 mIU/l, respectively) compared to OA (230.59Ī16.61 and 245.97Ī21.88 mIU/l, respectively, both p<0.05). Synovial fluid PRL levels correlate with DAS-28 (p=0.010) and serum PRL levels correlate with structural damage (p=0.014). 3. Genotype GT -1149 G/T SNP PRL is more frequent in RA than in controls, pc =0.039; OR 1.82. Genotype GG is more common in patients with onset of SLE at the age of 21 – 40 years compared to other disease onsets, pc =0.023; OR 2.94. Similarly, the TT genotype seems to be rare in SSc with disease onset after 45th year of age compared to patients with disease onset prior 45 years of age, pc =0.02; OR 0.13. Conclusion: This is the first immunogenetic study in two severe rheumatic diseases - SLE and PsA in the Czech population. We detected that the allele MIC-A5.1 incerases the risk for the development of SLE in HLA-DRB1*03 individuals. The allele HLA-Cw*0602 is a risk factor for PsA with psoriasis type I. PRL modulates the course of systemic rheumatic diseases: PRL reflects the activity and severity of RA, and alleles of -1149G/T SNP PRL gene show differences associated with the age at disease onset of SLE and SSc.

• Klíčová slova
• polymorfismus, alela, gen,
• MeSH
• alely MeSH
• autoimunita genetika   MeSH
• autoimunitní nemoci genetika   imunologie   MeSH
• biologické markery krev   MeSH
• financování organizované MeSH
• genotypizační techniky MeSH
• HLA-D antigeny genetika   imunologie   krev   MeSH
• imunogenetické jevy MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• MHC antigeny I. třídy genetika   imunologie   krev   MeSH
• MHC antigeny II. třídy genetika   imunologie   krev   MeSH
• polymerázová řetězová reakce MeSH
• prolaktin imunologie   krev   MeSH
• psoriatická artritida diagnóza   etiologie   genetika   MeSH
• radioimunoanalýza MeSH
• revmatoidní artritida diagnóza   etiologie   genetika   MeSH
• sexuální faktory MeSH
• statistika jako téma MeSH
• studie případů a kontrol MeSH
• synoviální tekutina chemie   MeSH
• systémová sklerodermie genetika   MeSH
• systémový lupus erythematodes dietoterapie   etiologie   genetika   MeSH
• věk při počátku nemoci MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH