Regulace pomocí cytokinové signální sítě významnou měrou ovlivňuje homeostázu, fyziologické funkce buněk a uplatňuje se při rozvoji řady patologických stavů, včetně nádorových onemocnění. Pomocí imunoanalytické metody ELISA autoři stanovili hladiny vybraných cytokinů a kostimulačních molekul v plazmě 30 dárců krve. Věk dárců se pohyboval od 19 do 52 let (medián 30,5; ženy 29, muži 32). Většina hladin interleukinů byla pod detekčním limitem metody. Vyhodnocení analýz bylo proto rozděleno na 2 části zvlášť pro interleukiny 2, 4, 5, 6, 8, 10, 13 a zvlášť pro ostatní sledované cytokiny a kostimulační molekuly (faktor nekrotizující tumory-α, transformující růstový faktor β1, solubilní CD23, CD40 ligand a receptor pro interleukin-6). Vztahy mezi jednotlivými parametry byly ověřovány Fisherovým exaktním testem v kontingenčních tabulkách. Pro jednotlivé interleukiny byly určeny pravděpodobnosti výskytu měřitelných hodnot ve zdravé populaci, včetně intervalu spolehlivosti pro tuto pravděpodobnost. Zjištěné hodnoty jsou výchozí referenční hodnoty pro shodné sledování hladin cytokinů u pacientů s diagnostikovanými hematologickými malignitami. Cytokinová či anticytokinová terapie s využitím monoklonálních protilátek je rovněž již součástí léčby řady nenádorových i nádorových onemocnění.
Homeostasis and cell functions are remarkably influenced by cytokine signal network. Cytokine regulation is involved in many diseases, including cancer. ELISA method was used for the detection of soluble cytokines and co-stimulatory molecules in plasma of 30 blood donors in age range from 19 to 52 years (median 30,5; women 29, men 32). Most of the interleukin concentrations were below the detection limit of the assay. Because of problem of “zero” values (below detection limits), separate data evaluation of interleukin and other cytokine and co-stimulatory molecules (tumor necrosis factor-α, transforming growth factor β1, soluble CD23, CD40 ligand and IL-6 receptor) was made. Dependency between the parameters was tested using the Fisher’s exact tests for contingency table. The probability of the occurrence at detactable level for each particular interleukin was calculated, including the confidence interval for the probability. These results provide fundamental reference values of cytokine concentrations in plasma for identical observations on the patients with hematological malignancies. The cytokine or anti-cytokine therapy has already become a part of therapeutic protocols in treatment of malignant and non-malignant diseases.
- MeSH
- Cytokines analysis physiology blood MeSH
- Blood Donors MeSH
- Enzyme-Linked Immunosorbent Assay methods utilization MeSH
- Research Support as Topic MeSH
- Hematologic Neoplasms genetics immunology blood MeSH
- Humans MeSH
- Antibodies, Monoclonal isolation & purification blood therapeutic use MeSH
- Check Tag
- Humans MeSH
CD30/CD30L and CD40/CD40L are molecules from the tumor necrosis factor (TNF) superfamily. They have a major effect on communications between the B and T cells, which leads to control of maturation, proliferation, and apoptosis of those cells. The aim of this study was to compare the levels of a soluble form of CD30 (sCD30) and a soluble ligand CD40 (sCD40L) in patients with systemic lupus erythematosus (SLE) (n=65) and healthy controls (sCD30 n=20, sCD40L n=10) with other parameters of SLE activity. Patients were divided into subgroups according to presence or absence of lupus nephritis (LN; 33 with LN, 32 without LN). The serum levels of selected parameters were assessed also in the subgroups with low active disease characterized by European Lupus Activity Measure (ECLAM) at most 3(n=29) and active disease with ECLAM more than 3 (n=36). The serum levels of sCD30 were 66.0+/-40.2 UI/ml in the whole group. The mean serum levels were 60.0+/-45.2 UI/ml in the subgroups with LN, 67.1+/-38.9 UI/ml in the subgroup without LN, 80.2+/-51.9 UI/ml in the subgroup with active disease, 55.4+/-24.1 UI/ml in the subgroup with low active disease, and finally, 40.1+/-19.2 U/ml in the controls. Significant differences were found between the SLE patients and controls (p=0.0001) and between the active and nonactive groups (p=0.002). A correlation was found between levels of CD30 and ECLAM (r=0.25, p
- MeSH
- Ki-1 Antigen blood MeSH
- Biomarkers blood MeSH
- Adult MeSH
- Financing, Organized MeSH
- Middle Aged MeSH
- Humans MeSH
- CD40 Ligand blood MeSH
- Adolescent MeSH
- Aged MeSH
- Lupus Erythematosus, Systemic diagnosis blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
Cíl práce: Otestovat klinickou způsobilost nových biomarkerů predikovat výskyt koronární restenózy po PCI u diabetických pacientů se stabilními formami ischemické choroby srdeční. Metodika: Soubor tvoří 27 pacientů s diabetes mellitus 2. typu a stabilní formou ischemické choroby srdeční, kteří se podrobili perkutánní koronární intervenci (PCI) v letech 2007–2008. Před procedurou, za jeden měsíc a za šest měsíců po PCI bylo provedeno klinické vyšetření, laboratorní stanovení běžných biochemických parametrů a odběry krevních vzorků ke stanovení ul trasenzitivního CRP (hsCRP), solubilního ligandu CD40 (sCD40L) a monocytárního chemoatraktivního proteinu-1 (MCP-1). Po šesti měsících byla provedena kontrolní koronarografi e a pomocí kvantitativní koronární analýzy (QCA) vyhodnocena přítomnost angiografi cké restenózy. Výsledky: Restenóza byla defi nována jako přítomnost opětovného zúžení > 50 % lumen tepny ve srovnání s výchozím stavem po PCI a byla detekována u 12 pacientů. Nebyl přítomen signifi kantní rozdíl v koncentraci hsCRP mezi pacienty bez restenózy a s restenózou před PCI (2,7 vs. 4,0; p = 0,093), jeden měsíc po PCI (1,2 vs. 1,3; p = 0,548) a šest měsíců po PCI (2,5 vs. 1,2; p = 0,347). Při srovnání obou podskupin nebyl přítomen ani signifi kantní rozdíl v koncentraci sCD40L před PCI (11,9 vs. 11,0; p = 0,867), jeden měsíc po PCI (8,3 vs. 8,2; p = 0,829) a šest měsíců po PCI (2,5 vs. 1,2; p = 0,905). Nebyl přítomen ani signifi kantní rozdíl v koncentraci MCP-1 před PCI (270,2 vs. 274,8; p = 0.683), jeden měsíc po PCI (316,0 vs. 338,0; p = 0,648) a šest měsíců po PCI (311,0 vs. 290,8; p = 0,755). Závěr: V rámci pilotního projektu jsme na malém souboru neprokázali význam sérové koncentrace hsCRP, sCD40L a MCP-1 pro predikci in-stent restenózy u diabetiků 2. typu.
Aim of study: To test the possibility of predicting development of restenosis in patients with type-2 diabetes mellitus using selected infl ammatory markers. Method: The group comprised 27 patients with type-2 diabetes mellitus and stable coronary heart disease undergoing percutaneous coronary intervention (PCI) in 2007–2008. Prior to the procedure and at one and six months post-procedurally, the patients had clinical examination, laboratory investigations to measure common biochemical parameters, and blood sampling for high-sensitive CRP (hsCRP), soluble ligand CD40 (sCD40L), and monocyte chemoattractant protein-1 (MCP-1) determination. At six months, patients had follow-up coronary angiography to identify any restenosis using quantitative coronary analysis (QCA). Results: Restenosis is defi ned as the presence of repeat narrowing > 50% of the arterial luminal diameter compared with post-PCI baseline value. Restenosis was detected in 12 patients. There was no signifi cant diff erence in hsCRP levels between patients with and without restenosis before PCI (2.7 vs. 4.0; p = 0.093), and one month (1.2 vs. 1.3; p = 0.548) and six months after PCI (2.5 vs. 1.2; p = 0.347). When comparing both subgroups, no signifi cant diff erence was also found in sCD40L levels before PCI (11.9 vs. 11.0; p = 0.867), and one month (8.3 vs. 8.2; p = 0.829) and six months post-PCI (2.5 vs. 1.2; p = 0.905). Likewise, no signifi cant diff erence was present in MCP-1 levels prior to PCI (270.2 vs. 274.8; p = 0.683), and one month (316.0 vs. 338.0; p = 0.648) and six months (311.0 vs. 290.8; p = 0.755). Conclusion: Our pilot project involving a small number of patients did not demonstrate any value of the serum levels of hsCRP, sCD40L a MCP-1 for predicting in-stent restenosis in patients with type-2 diabetes.
- Keywords
- Zánětlivé markery, hsCRP, sCD40L, MCP-1,
- MeSH
- Angioplasty, Balloon, Coronary methods adverse effects utilization MeSH
- Biomarkers blood MeSH
- C-Reactive Protein immunology isolation & purification MeSH
- Chemokine CCL2 immunology isolation & purification MeSH
- Diabetes Mellitus, Type 2 diagnosis complications MeSH
- Financing, Organized MeSH
- Myocardial Ischemia diagnosis complications MeSH
- Coronary Angiography methods utilization MeSH
- Coronary Restenosis diagnosis prevention & control MeSH
- Coronary Stenosis diagnosis surgery complications MeSH
- Humans MeSH
- CD40 Ligand immunology isolation & purification MeSH
- Inflammation Mediators immunology isolation & purification MeSH
- Monocyte Chemoattractant Proteins immunology isolation & purification MeSH
- Pilot Projects MeSH
- Retrospective Studies MeSH
- Statistics as Topic MeSH
- Outcome and Process Assessment, Health Care MeSH
- Check Tag
- Humans MeSH
Cílem sdělení je poskytnout přehled základních charakteristik některých biomarkerů, které mají potenciál klinického užití v diagnostice a stratifikaci rizika pacientů s akutními koronárními syndromy a se srdečním selháním. Jsou to markery myokardiální ischemie a nekrózy (troponin T a I, kreatinkináza, novější ischemií modifikovaný albumin, mastné kyseliny vážící protein A, cholin, enzym glykogenfosforylázy BB, pregnancy associated protein, placentární růstový faktor, solubilní CD40 ligand) a markery myokardiální funkce (natriuretické peptidy). Autoři podávají základní přehled o těchto parametrech doplněný jejich možným využitím v klinické praxi či v oblasti výzkumu. Klíčová slova: biomarkery, nekróza myokardu, ischemie myokardu, troponin, kreatinkináza, cholin, ischemií modifikovaný albumin, mastné kyseliny vážící protein, pregnancy associated protein A, sCD40L, placentární růstový faktor, natriuretické peptidy, glykogenfosforyláza BB.
The purpose of this review is to provide an overview of essential clinical characteristics of several biomarkers that may have a potential clinical utility in diagnosing process and risk stratification in patients with acute coronary syndromes and heart failure. These biomarkers belong to those, which can detect myocardial ischemia and necrosis (troponin T and I, creatinkinase, ischemia-modified albumin, fatty acids binding protein, choline, glycogen phoshorylase isoenzyme BB, placental growth hormone, pregnancy-associated protein A, soluble CD40 ligand) and markers of myocardial function (natriuretic peptides). Authors reveal essential summary of these parameters enriched with the possible use of these parameters in clinical practice and research. Key words: biomarkers, myocardial necrosis, myocardial ischemia, troponincreatinkinase, ischemia-modified albumin, fatty acids binding protein, choline, glycogen phoshorylase isoenzyme BB, placental growth hormone, pregnancy-associated protein A, sCD40L, natriuretic peptides.
- MeSH
- Biomarkers MeSH
- Choline blood MeSH
- Financing, Government MeSH
- Myocardial Infarction diagnosis blood MeSH
- Myocardial Ischemia blood MeSH
- Creatine Kinase blood MeSH
- Humans MeSH
- CD40 Ligand MeSH
- Glycogen Phosphorylase, Brain Form analysis MeSH
- Natriuretic Peptides analysis MeSH
- Necrosis blood MeSH
- Serum Albumin analysis MeSH
- Pregnancy-Associated Plasma Protein-A analysis MeSH
- Troponin MeSH
- Check Tag
- Humans MeSH
Súčasný výskum sa sústredí na molekuly, ktorými by sme mohli detekovať skoršie štádiá akútnych koronárnych syndrómov ako sme schopní s troponínmi. Solubilný CD40L predstavuje unikátne spojenie medzi trombózou a lokálnym zápalovým procesom. Podľa klinických údajov sú jeho zvýšené hladiny spojené s vysokým rizikom smrtelného infarktu myokardu, chronického srdcového zlyhania alebo rekurentného infarktu u pacientov s akútnym koronárnym syndrómom. Mohol by odhaliť pacientov, ktorí by profitovali z terapie IIb/IIIa antagonistami a stratifikovať riziko trombózy pred plánovanou implantáciou stentu. K definitívnemu stanovisku sú potrebné ďalšie štúdie.
Current research is focused on the new cardiac markers that allow detect earlier stages of acute coronary syndromes than is possible with troponins. One of the most promising is CD40 ligand. Clinical data showed that higher levels of sCD40L are associated with a high risk of cardiovascular events. Elevation of soluble CD40 ligand identifies the subgroup of patients who are likely to benefit from antiplatelet treatment with IIb/IIIa antagonists. This marker can be usefull for the assessment of risk stratification before planning stent implantation. Future investigation should include large, well-designed prospective observational cohort studies of patients in risk of ACS in order to evaluate the performance of sCD40L as a diagnostic test for ACS.
Introduction. Since atherosclerosis may in part be an inflammatory disease, circulatory factors related to inflammation may be predictors of coronary artery disease. The aim of this study was to evaluate the association between the level of some circulating biomarkers and the extent of coronary artery disease. Methods. Blood samples were taken from 128 patients with stable forms of coronary heart disease. Macrophage chemoattractant protein-1 (MCP-1), matrix-metalloproteinase-3 (MMP-3), soluble CD40 ligand (sCD40L) and soluble tumour necrosis factor receptor-2 (sTNFR2) were measured by ELISA. Coronary angiography and grading with the SYNTAX score followed. Results. There was no significant interdependence of circulating MCP-1, sCD40L, sTNFR2 levels and SYNTAX score. MMP-3 levels were significantly different in subgroup with coronary artery disease (SYNTAX score > 0): 38.1 µg/l (13.6; 84.1) and subgroup without coronary artery disease (SYNTAX score = 0): 20.4 µg/l (13.1; 82.8), p=0.001. According to the Spearman correlation coefficient there was significant association between MMP-3 level and SYNTAX score (0.358, a=0.05). Conclusions. Our data suggest association between the extent of coronary artery disease and circulating MMP-3. We failed to demonstrate any association with the other investigated biomarkers.
- MeSH
- Biomarkers blood MeSH
- Chemokine CCL2 blood MeSH
- Financing, Organized MeSH
- Middle Aged MeSH
- Humans MeSH
- CD40 Ligand blood MeSH
- Matrix Metalloproteinase 3 blood MeSH
- Coronary Artery Disease diagnosis blood MeSH
- Receptors, Tumor Necrosis Factor, Type II blood MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
Cytokine production and immune activation are associated with various pathological conditions including neurodegenerative disorders. One of them is multiple sclerosis (MS), known autoimmune disease. Inflammatory changes were also reported in normal pressure hydrocephalus (NPH), neurodegenerative disorder, which pathophysiology remains still unclear. The aim of this research was to compare the group of MS subjects with NPH patients and controls and to evaluate the potential inflammatory substance of NPH in comparison with autoimmune inflamed MS. METHODS: The levels of IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40L and TNF-α were measured in cerebrospinal fluid (CSF) and plasma in subjects with MS (n=15), NPH (n=18) and controls (n=11) by multiplex assay. RESULTS: The increased levels of IL-1β, IL-6, IL-10, IL-21 and TNF-α in cerebrospinal fluid of NPH subjects in comparison with MS patients and controls were found. Regarding the MS patients, we have confirmed increased IL-33 levels in cerebrospinal fluid and periphery as well as the increase of IL-1β and IL-10 in cerebrospinal fluid and IL-4 and sCD40L in plasma. CONCLUSION: The enlarged brain ventricles in NPH may repress and activate brain structures to the production of IL-1β, IL-6, IL-10, IL-21 and TNF-α, reflecting the inflammatory basis in NPH affected brain. The elevation of the above mentioned cytokines in MS was confirmed.
