AIMS: The present study aimed to assess vitamin D status and serum concentrations of pro-inflammatory cytokines IL-17, Il-23, and IL-18 in patients with chronic plaque psoriasis and their association with various demographic and clinical characteristics. METHODS: The study was conducted during the autumn/winter period on 48 patients with chronic plaque psoriasis and 48 controls. Total serum 25(OH)D level was determined with Roche Elecsys® 2010 Vitamin D total assay. Commercial ELISA kits were used for quantifying the serum levels of IL-17A, IL-18, and IL-23. RESULTS: Serum 25(OH)D had a median value of 16.95 ng/mL (IQR 10.8-23.50) for patients with psoriasis and 18.80 ng/mL (IQR 15.45-25.85) for the control group (P=0.09). A moderate negative correlation was found between PASI score and 25(OH)D levels (rs=-0.34; P=0.02). The serum levels of IL-17 (P=0.001), IL-23 (P=0.01) and IL-18 (P=0.02) were significantly higher in the patient group compared to controls. IL-17 concentrations were higher in patients with moderate to severe psoriasis compared to patients with mild psoriasis (P=0.003). No significant correlations were detected between the serum concentrations of 25(ОH)D and IL-17, IL-23, and IL-18. CONCLUSION: It was confirmed that IL-17 serum level is associated with psoriasis severity. Measurement of 25(OH)D serum concentration can be useful in patients with moderate to severe psoriasis with or without comorbidities. A direct association between 25(OH)D serum concentration and the serum concentrations of IL-17, IL-23, or IL-18 was not identified in this study.
- MeSH
- Adult MeSH
- Interleukin-17 * blood MeSH
- Interleukin-18 * blood MeSH
- Interleukin-23 * blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Psoriasis * blood MeSH
- Case-Control Studies MeSH
- Vitamin D * blood analogs & derivatives MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Proinflammatory cytokines and their inhibitors are involved in the regulation of multiple immune reactions including response to transplanted organs. In this prospective study, we evaluated changes in serum concentrations of six IL-1 family cytokines (IL-1 alpha, IL-1 beta, IL-1RA, IL-18, IL-18BP, and IL-36 beta) in 138 kidney allograft recipients and 48 healthy donors. Samples were collected before transplantation and then after one week, three months and one year, additional sera were obtained at the day of biopsy positive for acute rejection. We have shown, that concentrations of proinflammatory members of the IL-1 family (IL-1β, IL-18, IL-36 β) and anti-inflammatory IL-18BP decreased immediately after the transplantation. The decline of serum IL-1RA and IL-1α was not observed in subjects with acute rejection. IL-18, including specifically its free form, is the only cytokine which increase serum concentrations in the period between one week and three months in both groups of patients without upregulation of its inhibitor, IL-18BP. Serum concentrations of calculated free IL-18 were upregulated in the acute rejection group at the time of acute rejection. We conclude that IL-1 family cytokines are involved mainly in early phases of the response to kidney allograft. Serum concentrations of free IL-18 and IL-18BP represent possible biomarkers of acute rejection, and targeting IL-18 might be of therapeutic value.
- MeSH
- Allografts * MeSH
- Biomarkers * blood MeSH
- Adult MeSH
- Transplantation, Homologous methods MeSH
- Interleukin-1 blood MeSH
- Interleukin-18 * blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Intercellular Signaling Peptides and Proteins blood MeSH
- Prospective Studies MeSH
- Graft Rejection * immunology blood MeSH
- Kidney Transplantation * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Critically ill patients suffer from acute muscle wasting, which is associated with significant physical functional impairment. We describe data from nested muscle biopsy studies from two trials of functional electrical stimulation (FES) that did not shown improvements in physical function. METHODS: Primary cohort: single-centre randomized controlled trial. Additional healthy volunteer data from patients undergoing elective hip arthroplasty. Validation cohort: Four-centre randomized controlled trial. INTERVENTION: FES cycling for 60-90min/day. ANALYSES: Skeletal muscle mRNA expression of 223 genes underwent hierarchal clustering for targeted analysis and validation. RESULTS: Positively enriched pathways between healthy volunteers and ICU participants were "stress response", "response to stimuli" and "protein metabolism", in keeping with published data. Positively enriched pathways between admission and day 7 ICU participants were "FOXO-mediated transcription" (admission = 0.48 ± 0.94, day 7 = - 0.47 ± 1.04 mean log2 fold change; P = 0.042), "Fatty acid metabolism" (admission = 0.50 ± 0.67, day 7 = 0.07 ± 1.65 mean log2 fold change; P = 0.042) and "Interleukin-1 processing" (admission = 0.88 ± 0.50, day 7 = 0.97 ± 0.76 mean log2 fold change; P = 0.054). Muscle mRNA expression of UCP3 (P = 0.030) and DGKD (P = 0.040) decreased in both cohorts with no between group differences. Changes in IL-18 were not observed in the validation cohort (P = 0.268). Targeted analyses related to intramuscular mitochondrial substrate oxidation, fatty acid oxidation and intramuscular inflammation showed PPARγ-C1α; (P < 0.001), SLC25A20 (P = 0.017) and UCP3 (P < 0.001) decreased between admission and day 7 in both arms. LPIN-1 (P < 0.001) and SPT1 (P = 0.044) decreased between admission and day 7. IL-18 (P = 0.011) and TNFRSF12A (P = 0.009) increased in both arms between admission and day 7. IL-1β (P = 0.007), its receptor IL-1R1 (P = 0.005) and IL-6R (P = 0.001) decreased in both arms between admission and day 7. No between group differences were seen in any of these (all p > 0.05). CONCLUSIONS: Intramuscular inflammation and altered substrate utilization are persistent in skeletal muscle during first week of critical illness and are not improved by the application of Functional Electrical Stimulation-assisted exercise. Future trials of exercise to prevent muscle wasting and physical impairment are unlikely to be successful unless these processes are addressed by other means than exercise alone.
Mortality and morbidity of newborns with sepsis can be improved by early and accurate diagnosis and targeted therapy. To evaluate the early molecular events associated with inflammation and infection, we evaluated markers of endothelial activation and injury and circulating plasma miRNAs in preterm newborns with sepsis. The study group consisted of newborns with gestational age ≤ 32 weeks, with culture-positive early-onset neonatal sepsis (sepsis group, N = 8), and as a control group, we enrolled newborns without sepsis (control group, N = 12). Soluble markers of inflammation were measured using Luminex-based multiplex assay. Platelet-free plasma RNA was used to construct the library for miRNA sequencing analysis. Normalized counts were calculated and used to measure differential expression of individual detected miRNAs. We found a significant increase of interleukin 18 (IL-18) in the cord blood of the sepsis group (mean ± SEM, 104.7 ± 30.4 pg/ml vs 52.7 ± 5.6 pg/ml, P = 0.02). In peripheral blood of sepsis group patients, we found a significant increase of VEGF-A compared to controls (196.0 ± 70.5 pg/ml vs 59.6 ± 8.5 pg/ml, P = 0.02). In the cord blood plasma, eight miRNAs had significantly differential expression (P < 0.05), four miRNAs were up-regulated and four miRNAs down-regulated. In peripheral blood plasma, all nine miRNAs with significant differential expression were up-regulated. In conclusion, in early-onset neonatal sepsis, IL-18 and VEGF-A might be considered in diagnostic workup. Early-onset sepsis in preterm newborns is associated with significant changes in the circulating miRNA pattern.
- MeSH
- Biomarkers metabolism MeSH
- Interleukin-18 MeSH
- Infant MeSH
- Humans MeSH
- MicroRNAs * genetics MeSH
- Infant, Newborn MeSH
- Neonatal Sepsis * diagnosis MeSH
- Sepsis * diagnosis genetics MeSH
- Vascular Endothelial Growth Factor A MeSH
- Inflammation MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Journal Article MeSH
Východiska: Dříve provedené studie hodnotily souvislost polymorfizmu IL-8 -251T>A a IL-18 -607C>A s rizikem karcinomu prsu v různých populacích, ale výsledky zůstávají nekonzistentní a neprůkazné. Provedli jsme tedy tuto metaanalýzu s cílem prozkoumat souvislosti. Metody: Komplexní vyhledávání literatury v databázích PubMed, EMBASE, Web of Science, Scopus, SciELO, SID, and CNKI z hlediska všech vhodných studií publikovaných do 1. října 2020. Pro hodnocení intenzity souvislosti byly použity souhrnné poměry šancí (odds ratio – OR) s 95% intervaly spolehlivosti (confidence interval – CI). Výsledky: Bylo vybráno celkem 12 studií případů a kontrol o polymorfizmu IL-8 -251T>A vč. 7 studií s 2 370 případy a 2 314 kontrolami a 5 studií o polymorfizmu IL-18 -607C>A s 900 případy a 882 kontrolami. Souhrnná data ukázala, že polymorfizmy IL-8 -251T>A (AT vs. TT: OR = 1,187; 95% CI 1,038–1,356; p = 0,012) a IL-18 -607C>A (A vs. T: OR = 1,205; 95% CI 1,055–1,377; p = 0,006; AA vs. TT: OR = 1,379; 95% CI 1,056–1,802; p = 0,018; a AA vs. AT+TT: OR = 1,329; 95% CI 1,053–1,678; p = 0,017) měly obecně souvislost se zvýšeným rizikem karcinomu prsu. Navíc když byly studie stratifikovány podle etnik, u IL-8 -251T>A byla významná souvislost s rizikem karcinomu prsu u Afričanek. Testy publikačního zkreslení u metaanalýzy žádné publikační zkreslení neprokázaly. Závěr: Tato metaanalýza odhalila, že polymorfizmus IL-8 -251T>A a IL-18 -607C>A je spojen s náchylností ke karcinomu prsu. Pro lepší vyhodnocení těchto asociací je ovšem třeba dalších multicentrických studií s různými etniky.
Background: Previous studies have evaluated the association of IL-8 -251T>A and IL-18 -607C>A polymorphisms with a risk of breast cancer in different populations, but the results remain inconsistent and inconclusive. Thus, we performed this meta-analysis to explore the associations. Methods: A comprehensive literature search in PubMed, EMBASE, Web of Science, Scopus, SciELO, SID, and CNKI for all eligible studies published up to October 1, 2020. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the intensity of associations. Results: A total of 12 case-control studies including seven studies with 2,370 cases and 2,314 controls on IL-8 -251T>A, and five studies with 900 cases and 882 controls on IL-18 -607C>A polymorphism were selected. Pooled data showed that IL-8 -251T>A (AT vs. TT: OR= 1.187; 95% CI 1.038–1.356; P = 0.012) and IL-18 -607C>A polymorphisms (A vs. T: OR = 1.205; 95% CI 1.055–1.377; P = 0.006; AA vs. TT: OR = 1.379; 95% CI 1.056–1.802; P = 018; and AA vs. AT+TT: OR = 1.329; 95% CI 1.053–1.678; P = 0.017) were associated with increased risk of breast cancer in overall. Moreover, when the studies were stratified by ethnicity, the IL-8 -251T>A was significantly associated with breast cancer risk in Africans. Publication bias tests provide no evidence of presence of publication bias in a meta-analysis. Conclusion: This meta-analysis results revealed that the IL-8 -251T>A and IL-18 -607C>A polymorphisms are associated with susceptibility to breast cancer. However, further multicenter studies with larger sample sizes in different ethnicities are required to make a better assessment of these associations.
Stillova nemoc dospělých (adult onset StiLL's disease, AOSD) je choroba totožná se Stillovou chorobou dětí, systémovou formou juvenilní idiopatické artritidy (SJIA). Na rozdíl od dětské formy se manifestuje v mladém dospělém věku, výjimkou ale nejsou ani pozdější manifestace. Jedná se o prototyp nedědičné, sporadické formy systémového onemocnění na pomyslné křižovatce mezi autoinflamatorními a autoimnitními chorobami. Stillova nemoc dospělých patří mezi vzácné choroby, které se označují anglickým termínem „orphan diseases". Mechanismy vzniku choroby, jakož i jejího častého periodického charakteru spočívají v poruchách jak vrozené, tak adaptivní imunitní odpovědi. Mezi základní projevy choroby patří vysoké horečky, muskuloskeletální postižení, kožní manifestace a vysoké počty leukocytů s převahou neutrofilů. Existují dva navzájem se překrývající klinické fenotypy choroby, systémový typ manifestující se zejména horečkou, vyrážkou a postižením vnitřních orgánů a artikulární typ podobný více revmatoidní artritidě. Mimo výrazné neutrofilní leukocytózy se u akutního vzplanutí AOSD nacházejí prakticky vždy vysoké koncentrace reaktantů akutní fáze, časté jsou rovněž elevace aktivity jaterních enzymů. Poměrně charakteristickým nálezem bývá hyperferitinemie, která je indikátorem aktivace makrofágů. Choroba může probíhat velmi těžce. Relativně častou příčinou závažného orgánového postižení či úmrtí může být syndrom aktivovaných makrofágů (macrophage activation syndrome, MAS). Mezi další emergentní komplikace AOSD patří diseminovaná intravaskulární koagulace s kombinací krvácivých i trombotických manifestací či trombotická mikroangiopatie. Mezi vzácnější příčiny těžkého průběhu AOSD pak patří jaterní selhání, kardiopulmonální manifestace či amyloidóza. Za lék první volby byly u AOSD dosud považovány glukokortikoidy. Jejich nasazení vede k dobré klinické odpovědi asi u 60 % nemocných během několik dní. Nejčastěji podávaným chorobu modifikujícím lékem u AOSD je methotrexát, a to zejména pro svůj glukokortikoidy šetřící účinek. Současným pokrokem v léčbě AOSD je použití inhibitorů interleukinu (IL) 1 (anakinra, canakinumab), a to při závažných život ohrožujících formách nemoci i jako léčba první volby předcházející zahájení podávání glukokortikoidů. Alternativou může být léčba inhibitory IL-6 (tocilizumab, sarilumab). Inhibitory tumor nekrotizujícího faktoru a (tumor necrosis factor a, TNF-a) lze v současnosti považovat za léčbu třetí linie, údajů o jejich účinnosti je poměrně málo. Jako perspektivní směr v léčbě AOSD se pak jeví výzkum role inhibice IL-18.
Adult onset Still's disease (AOSD) is a disease practically identical to Still's children's disease, a systemic form of juvenile idiopathic arthritis (SJIA). It usually manifests at a young adult age, but later manfestations are no exception. It is a prototype of a non-hereditary, sporadic form of systemic disease at the imaginary crossroads between autoinflammatory and autoimmune diseases. AOSD is one of the rare diseases referred to by the term “orphan diseases”. The mechanisms of the disease, as well as its frequent periodic nature, lie in disorders of both the innate and adaptive immune responses. The basic manifestations of the disease include high fevers, musculoskeletal disorders, skin manifestations and marked neutrophilic leukocytosis. There are two overlapping clinical phenotypes of the disease, a systemic type manifested mainly by fever, rash and internal organ involvement, and an articular type similar to rheumatoid arthritis. In addition to neutrophilia, there are almost always increased levels of acute phase reactants in acute flares of AOSD, and elevations in liver enzymes are also common. Hyperferritinemia, which is an indicator of macrophage activation, is a relatively characteristic even if not specific finding. The disease can be very severe. Macrophage activation syndrome (MAS) is a relatively common cause of severe organ impairment or death. Other emergent complications of AOSD include disseminated intravascular coagulation with a combination of bleeding and thrombotic manifestations or thrombotic microangiopathy. Rare complications of AOSD include hepatic failure, cardiopulmonary manifestations, or amyloidosis. Glucocorticoids have so far been considered the drug of first choice in AOSD. Their use leads to a good clinical response in about 60% of patients within a few days. Methotrexate is the most commonly administered disease-modifying drug in AOSD, especially for its glucocorticoid-sparing effect. Recent advances in the treatment of AOSD include the use of interleukin 1 (IL-1) inhibitors (anakinra, canakinumab), both in severe life-threatening forms of the disease could be considered as a first-line treatment prior even to the use of glucocorticoids. Alternatively, treatment with IL-6 inhibitors (tocilzumab, sarilumab) could be also administered. Tumor necrosis factor a (TNF-a) inhibitors are currently considered as third-line treatment, there are relatively few data on their efficacy. Research into the role of IL-18 inhibition in therapy of AOSD is a promising direction of development.
- Keywords
- Anakinra, Rilonacept, Canakinumab,
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal administration & dosage therapeutic use MeSH
- Glucocorticoids administration & dosage therapeutic use MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Interleukin-1 antagonists & inhibitors MeSH
- Interleukin-18 antagonists & inhibitors MeSH
- Interleukin-6 antagonists & inhibitors MeSH
- Humans MeSH
- Methotrexate administration & dosage therapeutic use MeSH
- Receptors, Interleukin-1 antagonists & inhibitors MeSH
- Still's Disease, Adult-Onset * diagnosis epidemiology classification physiopathology therapy MeSH
- Tumor Necrosis Factor-alpha antagonists & inhibitors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Apolipoprotein J (clusterin) is a component of high-density lipoproteins, the high level of which is reversely correlated with the risk of coronary heart disease. In addition, it exerts anti-inflammatory and anti-apoptotic effects on endothelial cells and inhibits smooth muscle cell migration and proliferation, indicating that it may play a protective role in cardiovascular disease. However, the exact mechanisms by which this occurs remain unclear. This study aimed to clarify these underlying protective mechanisms by researching the inhibitory effects of apolipoprotein J via the NOD-like receptor protein 3 pathway on the inflammation induced by cholesterol crystals in THP‐1 macrophages. In culture, THP-1 macrophages were infected with adenoviral vectors containing apolipoprotein J genes and subsequently treated with cholesterol crystals. The inflammatory cytokines interleukin‐1β, interleukin 18 and tumour necrosis factor α were quantitatively measured with ELISA kits. NOD-like receptor protein 3, cysteinyl aspartate specific proteinase 1 and interleukin 1β were evaluated by Western blot and PCR analysis. As a result, apolipoprotein J expression was found to remarkably decrease the levels of inflammatory cytokines, including tumour necrosis factor α, interleukin 18 and interleukin 1β, secreted by THP‐1 macrophages. It was also found capable of inhibiting the levels of NOD-like receptor protein 3, cysteinyl aspartate-specific proteinase 1 and interleukin 1β both at the protein and mRNA levels. In the current study, we revealed that over-expression of apolipoprotein J attenuated the inflammation induced by cholesterol crystals through inhibition of the NOD-like receptor protein 3 inflammasome pathway.
- MeSH
- Cholesterol metabolism MeSH
- Cytokines metabolism MeSH
- Endothelial Cells metabolism pathology MeSH
- Inflammasomes * metabolism pharmacology MeSH
- Interleukin-18 metabolism MeSH
- Interleukin-1beta metabolism MeSH
- Clusterin metabolism pharmacology MeSH
- Aspartic Acid metabolism pharmacology MeSH
- Humans MeSH
- Macrophages metabolism MeSH
- Peptide Hydrolases metabolism pharmacology MeSH
- NLR Family, Pyrin Domain-Containing 3 Protein * metabolism MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Inflammation pathology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
This study aimed at evaluating the role played by insulin resistance, lipid metabolism disorder, oxidative stress, resistin, vaspin, Interleukin-18 and asymmetric dimethyl arginine as a marker for endothelial dysfunction in the pathogenesis of preeclampsia. This prospective observational cohort study involved 60 women who were classified into: 20 non-pregnant women (group 1 or control group), 20 normally pregnant women (group 2) and 20 preeclamptic women (group 3) at their third trimester. The pregnant women were assessed at their third trimester and further re-evaluated four weeks after delivery. The assessment included demography, assessment of proteinuria and urinary protein to creatinine ratio, blood pressure measurement and assessment of fasting blood glucose, fasting insulin level, lipid panel and the circulating levels of malondialdehyde, resistin, vaspin, interleukin-18 and asymmetric dimethyl arginine. Preeclamptic women showed more atherogenic lipid profile, significantly higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and significantly elevated levels of malondialdehyde, resistin, vaspin and interleukin-18 than the other study groups. Serum asymmetric dimethyl arginine concentration showed non-significant difference among the three study groups. The levels of resistin and vaspin showed significant decrease four weeks postpartum in preeclamptic group. We concluded that, preeclampsia was associated with insulin resistance, dyslipidemia, oxidative stress, inflammation and significant changes in adipokines; resistin and vaspin. Furthermore, the significant increase in the serum levels of resistin and vaspin at the third trimester and their significant decline four weeks postpartum in preeclamptic group focus the attention on the role played by these adipokines in the pathogenesis of preeclampsia.
Renální insuficience je spojena s četnými komorbiditami a zvýšenou mortalitou. Je třeba rozlišit chronické onemocnění ledvin (CKD – chronic kidney disease) od akutního poškození ledvin (AKI – acute kidney injury) a prerenálního AKI. K tomu by mohly sloužit novější markery AKI, především lipokalin asociovaný s želatinázou neutrofilů (NgAL), cystatin C, N-acetyl-β-D-glukosaminidáza (NAg), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP). Doporučuje se spíše jejich vyšetření v moči, prediktivní hodnota je pravděpodobně vyšší u dětí. Vzhledem k jejich nedostatečné senzitivitě a specificitě se považuje za vhodné vyšetřovat kombinaci dvou z nich. Za nejnadějnější je považováno stanovení močového NgAL, resp. jeho monomerické formy pocházející z renálních epitelií. Sérový kreatinin je nejčastěji vyšetřovaný nefrologický marker, k jeho vzestupu ale dochází relativně pozdě. V diagnostice renální insuficience však v klinické praxi stále sehrává nejdůležitější roli, je podkladem odhadu glomerulární filtrace (gF). Jeho stanovení, jak Jaffého metodou, tak enzymově, musí být spojené s udáním hodnoty gF a návazné na referenční systém. Při odhadu gF z enzymově stanoveného kreatininu musíme brát v potaz, že právě tato přesnější metoda poskytuje vyšší hodnoty ve srovnání s Jaffého metodou v oblasti vyšších koncentrací kreatininu (> 250 μmol/l). To může mít závažné diagnostické důsledky (směřující k časnějšímu zahájení dialýzy) především u dětských pacientů, kdy ve Schwartzově vzorci pro enzymový kreatinin navíc figuruje jednotný a nižší faktor F. Za nejvýznamnější ukazatel poškození ledvin v případě CKD je považována albuminurie. Imunochemické metody nezachytí tzv. imunonereaktivní albumin. Kvůli němu je albuminurie především u diabetiků v oblasti A1 podhodnocována, a to i přes návaznost metody na referenční systém.
Renal insufficiency is associated with numerous comorbidities and increased mortality. A distinction should be made between chronic kidney disease (CKD), acute kidney injury (AKI) and prerenal AKI. Newer AKI markers could be used, especially neutrophil gelatinase-associated lipocalin (NgAL), cystatin C, N-acetyl-β-D-glucosaminidase (NAg), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP). The examination of them is recommended mostly in urine, the predictive value is probably higher in children. Due to their lack of sensitivity and specificity, it is considered appropriate to investigate a combination of two of them. The most promising is considered the determination of urinary NgAL, resp. its monomeric form derived from renal epithelium. Serum creatinine is the most frequently investigated nephrological marker, but its increase occurs relatively late. However, it still plays the most important role in the diagnosis of renal insufficiency in clinical practice, it is the basis for the estimation of glomerular filtration (gF). Its determination, both by the Jaffe method and enzymatically, have to be linked to the indication of the gF value and to the reference system. when estimating gF from enzymatically determined creatinine, we have to take into account that this more accurate method provides higher values compared to the Jaffe method in the area of higher creatinine concentrations (> 250 μmol/L). This can have serious diagnostic consequences (leading to earlier start of dialysis), especially in pediatric patients, where the Schwartz formula for the enzymatical creatinine includes a uniform and lower factor F in addition. Albuminuria is considered to be the most important marker of renal damage in CKD. Immunochemical methods do not capture so-called immuno-unreactive albumin. Due to this, albuminuria is underestimated, especially in diabetics in the A1 area, despite the method’s connection to the reference system.
Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms in IL-1 gene cluster, IL-6 and its receptor, IL-10, IL-17A, and IL-18 were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphism IL‐10-1087 A/G (rs1800896) and specific IL-10 haplotypes were associated with the development of the disease (P < 0.05, Pcorr > 0.05). Four bacterial species occurred more frequently in AgP than in controls (P < 0.01, Pcorr < 0.05). Elevated IL-10 levels were found in AgP patients, carriers of IL‐10-1087GG genotype, and PBMCs stimulated by periodontal bacteria (P < 0.05, Pcorr > 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression of IL-10 and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.
- MeSH
- Aggressive Periodontitis genetics immunology microbiology MeSH
- Alleles MeSH
- Bacteria genetics MeSH
- Adult MeSH
- Gene Frequency genetics MeSH
- Genetic Predisposition to Disease genetics MeSH
- Genotype MeSH
- Haplotypes genetics MeSH
- Interleukin-1 genetics MeSH
- Interleukin-10 genetics MeSH
- Interleukin-17 genetics MeSH
- Interleukin-18 genetics MeSH
- Interleukin-6 genetics MeSH
- Interleukins genetics metabolism MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Humans MeSH
- Periodontitis genetics immunology MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
