Systémová forma juvenilní idiopatické artritidy (sJIA) je charakterizována systémovým zánětem, který se projevuje rekurentní horečkou, kožní vyrážkou, hepatosplenomegalií, lymfadenopatií, serozitidou, artritidou a elevací laboratorních zánětlivých parametrů. Život ohrožující komplikací může být syndrom aktivace makrofágů (macrophage activation syndrome, MAS). Zejména na začátku nemoci se v patogenezi sJIA uplatňuje dysregulace vrozené imunitní odpovědi s nadprodukcí interleukinu 1 (IL-1). Při léčbě blokátory IL-1 je prokázáno významné zlepšení průběhu i prognózy sJIA, a to zejména v případě včasného zahájení léčby. Anakinra, antagonista receptoru pro interleukin 1, je účinným lékem u pacientů se sJIA, což ukazuje i naše kazuistika.

Systemic juvenile idiopathic arthritis (sJIA) is characterized by systemic inflammation, which manifests itself with recurrent fever, skin rash, hepatosplenomegaly, lymphadenopathy, serositis, arthritis and elevated inflammatory markers. Macrophage activation syndrome (MAS) can be a life-threatening complication of this disease. Especially at disease onset, the dysregulation in the innate immune response with overproduction of interleukin 1 (IL-1) plays a key role in the pathogenesis of sJIA. Anti-IL-1 therapy significantly improves treatment outcomes and prognosis, particularly when initiated early. Anakinra, an interleukin-1 receptor antagonist, is an effective treatment option for patients with sJIA.

Psoriáza je systémové zánětlivé onemocnění s převahou projevů na kůži. Je charakterizována komplexní patofyziologií určenou genovou predispozicí s výrazným podílem faktorů vnitřního i vnějšího prostředí, které se uplatňují epigenetickými mechanismy. Podstatnou součástí je poškozující zánět, na který cílí různé léčebné modality. U většiny nemocných jimi lze dosáhnout zhojení kožních projevů, následované ale obvykle exacerbací onemocnění. Jednou z příčin exacerbace by mohla být tzv. zánětlivá jizva charakterizovaná abnormálním nastavením buněčných složek vrozené a specifické imunity i kůže. Na jejím vzniku a udržování se podílejí epigenetické procesy, které bude možné v blízké budoucnosti léčebně modulovat.

Psoriasis is a systemic inflammatory disease with clinical presentation on skin. Pathophysiology of psoriasis is complex with genetic predisposition and substantial contribution of variable factors of both internal and external origins which is mediated by epigenetic mechanisms. Immunopathological mechanisms are the target of the most effective therapeutical modalities with the ultimate goal „clean skin“. However, the therapeutical efficacy is lost in time in majority of patients. Exacerbation of skin presentation could be caused by so called „inflammatory scar“ characterized by abnormal setting of both innate and specific immunity cellular substrate together with participation of skin cells. Inflammatory scar initiation and duration is regulated largely by epigenetic mechanisms, which could be therapeuticaly modulated in near future.

Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterized by the persistent presence of antiphospholipid antibodies (aPL), and is commonly associated with thrombosis and pregnancy-related complications. To date, relatively little is known about the potential of NK cells in mediating the pathological effects of APS. While the role of NK cells in controlling immune responses and maintaining tissue homeostasis is relatively clear, the fact that they are also linked to various autoimmune conditions is now being highlighted. Given the impact of NK cells on immune regulation, vascular function, and pregnancy outcomes, the unifying message of a critical role for NK cells in APS emerges. As innate immune cells, NK cells might be activated in an antibody dependent manner and exert antibody-dependent cellular cytotoxicity (ADCC). In this process, NK cells recognize and bind to the Fc portion of antibodies that have attached to target cells. With their immunoregulatory properties in the uterus, NK cells play a crucial role in facilitating endometrial tissue remodeling, supporting vascular function, and contributing to placental formation, all of which are essential for a successful pregnancy. In APS, the presence of aPL may disrupt the delicate balance of NK cell-mediated immune regulation leading to alterations in cell activation, cytokine production, and cytotoxic functions. Given the multifactorial nature of NK cells in peripheral blood and uterus, the review provides insight into the potential underlying mechanisms through which NK cells may contribute to thrombosis and pregnancy complications in APS.

• MeSH
• antifosfolipidové protilátky imunologie   MeSH
• antifosfolipidový syndrom * imunologie   metabolismus   MeSH
• buněčná cytotoxicita závislá na protilátkách MeSH
• buňky NK * imunologie   metabolismus   MeSH
• komplikace těhotenství imunologie   MeSH
• lidé MeSH
• těhotenství MeSH
• trombóza imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Trained immunity is defined as an enhanced state of the innate system which leads to an improved immune response against related or non-related pathogens. Bacillus Calmette-Guérin (BCG) vaccine, a live attenuated Mycobacterium bovis strain, is currently one of the main inductors of trained immunity. The objective of the present study was to evaluate the protective effects of heat-inactivated M. bovis (HIMB) against Plasmodium berghei and Borrelia burgdorferi and characterize the immunological mechanisms involved. BALB/c and C3H/HeN mice were randomly assigned in similar number to either immunized group receiving two oral doses of HIMB with a 4-week interval, or control group treated with PBS. All the BALB/c mice were intraperitoneally infected with P. berghei while the C3H/HeN mice were subcutaneously infected with B. burgdorferi. Pathogen burden was significantly reduced in both immunized groups when compared to controls. The number of macrophages significantly decreased in the liver or in the spleen of the mice that had been immunized prior to the challenge with P. berghei or B. burgdorferi, respectively. Furthermore, the immunized groups showed an apparent upregulation of IFN-γ, TNF-α and IL-1α in the liver (P. berghei challenge) or a significant increase in IL-1α producing cells in the spleen (B. burgdorferi challenge). Our findings suggest that oral immunization with heat-inactivated mycobacteria limits pathogen burden through stimulation of the innate immune response in two vector-borne diseases in mice.

• MeSH
• adjuvancia imunologická * aplikace a dávkování   MeSH
• BCG vakcína * imunologie   aplikace a dávkování   MeSH
• Borrelia burgdorferi imunologie   MeSH
• cytokiny MeSH
• inaktivované vakcíny imunologie   aplikace a dávkování   MeSH
• interferon gama imunologie   MeSH
• interleukin-1alfa imunologie   MeSH
• játra imunologie   MeSH
• lymeská nemoc * prevence a kontrola   imunologie   MeSH
• makrofágy imunologie   MeSH
• malárie * prevence a kontrola   imunologie   MeSH
• Mycobacterium bovis * imunologie   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C3H MeSH
• myši MeSH
• Plasmodium berghei imunologie   MeSH
• protilátky bakteriální krev   MeSH
• slezina imunologie   mikrobiologie   MeSH
• TNF-alfa imunologie   MeSH
• vysoká teplota MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Východiská: Z hľadiska epidemiológie predstavuje kolorektálny karcinóm (KRK) celosvetovo jeden z najčastejšie sa vyskytujúcich nádorov. Pokrok vo výskume sa premietol do zníženia úmrtnosti na toto ochorenie, avšak zníženie veku vzniku KRK vytvára obavy vo väčšine rozvinutých krajín. Identifikácia a validácia účinných prognostických biomarkerov sú kľúčové pre zvýšenie presnosti diagnostiky a individualizáciu liečby. Cieľ: Cieľom práce je analyzovať najnovšie údaje o epidemiológii a rizikových faktoroch KRK. Naratívny prehľad sa zameriava aj na zhrnutie súčasných poznatkov o rôznych prognostických biomarkeroch pri liečbe KRK, vrátane ukazovateľov výkonnostného stavu, nutričných a zápalových markerov. Záver: KRK predstavuje závažný zdravotný problém vo väčšine krajín a nádorové biomarkery, ako aj stav pacienta pred liečbou, sú rozhodujúce pre určenie prognózy ochorenia. Ukazovatele nutričného a výkonnostného stavu zohrávajú zásadnú úlohu pri hodnotení stavu pacienta a ovplyvňujú rozhodnutia o liečbe, s potenciálnym dopadom na jej výsledky. Zápalové markery sa javia ako významný prognostický faktor, korelujúc s imunitnou odpoveďou pacienta na nádor a zápalovými procesmi, ktoré môžu viesť k progresii ochorenia. Napriek ich sľubnej prediktívnej sile sa tieto biomarkery zatiaľ bežne nepoužívajú v klinickej praxi z dôvodu potreby ďalšej vedeckej validácie. Integrácia nových biomarkerov do klinickej praxe by však mohla viesť k personalizovanejším liečebným stratégiam a tým k zlepšeniu prežívania pacientov. Pre komplexnejšie posúdenie validity týchto biomarkerov a ich aplikácie v bežnej klinickej praxi je potrebný ďalší výskum.

Background: In terms of epidemiology, colorectal carcinoma (CRC) represents one of the most prevalent tumors worldwide. Progress in research has translated into reduced mortality of the disease, but the trend of early onset CRC troubles most of the developed countries. Identification and validation of effective prognostic biomarkers are crucial for improving diagnostic accuracy and treatment outcomes. Purpose: The objective of the work is to analyze the latest data on the epidemiology and risk factors of CRC. A narrative review also aims to summarize current knowledge about various prognostic biomarkers in the treatment of CRC, including indicators of performance status, nutritional, and inflammatory markers. Conclusion: CRC pose major health problem in most of the countries and the tumor biomarkers as well as patients pre-treatment condition are crucial to establish prognosis of the disease. Nutritional and performance status indicators play an essential role in assessing the patient’s condition and influence treatment decisions, with a potential impact on treatment outcomes. Inflammatory markers have demonstrated significant prognostic value, correlating with the patient’s immune response to the tumor and inflammatory processes that may promote disease progression. Despite promising predictive capabilities, these biomarkers are not yet routinely used in clinical practice due to the need for further research validation. The integration of new biomarkers into clinical practice could lead to more personalized treatment decisions and improved treatment outcomes. For a more comprehensive assessment of the validity of these biomarkers and their application in regular clinical practice, further research is necessary.

• MeSH
• biologické markery MeSH
• fyziologie výživy MeSH
• genetické testování MeSH
• geny ras genetika   MeSH
• kolorektální nádory * epidemiologie   MeSH
• lidé MeSH
• mikrosatelitní nestabilita MeSH
• prognóza * MeSH
• protoonkogenní proteiny B-Raf genetika   škodlivé účinky   MeSH
• rizikové faktory * MeSH
• staging nádorů metody   MeSH
• zánět komplikace   patofyziologie   MeSH
• Check Tag
• lidé MeSH

Inflammatory bowel disease (IBD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). This article reviews the epidemiology, pathophysiology, risk factors and treatment implications of ASCVD in IBD patients. A number of processes are involved in the increased risk of ASCVD, including inflammation, endothelial dysfunction, hypercoagulability, platelet abnormalities, dyslipidaemia, gut microbiome abnormalities and the use of corticosteroids. While the precise pathophysiology remains complex, the management of inflammation and cardiovascular risk factors is essential to reduce the risk of atherosclerosis in IBD patients. Collaboration between gastroenterologists and preventive cardiologists is emphasised for risk factor management and promotion of disease remission.

• MeSH
• ateroskleróza * etiologie   MeSH
• biologické markery analýza   MeSH
• idiopatické střevní záněty * komplikace   patofyziologie   MeSH
• kardiovaskulární nemoci etiologie   MeSH
• lidé MeSH
• oxidační stres MeSH
• rizikové faktory MeSH
• zánět komplikace   patofyziologie   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: To determine differences in the blood innate gene expression signatures of systemic lupus erythematosus (SLE) patients across various organ manifestations and disease activity, with a focus on lupus nephritis (LN) and central nervous system (CNS) involvement. METHODS: Toll-like receptor family (TLR 1-10) mRNA expression was investigated in peripheral blood mononuclear cells from patients with SLE (n = 74) and healthy controls (n = 34). We compared patients with histologically confirmed active LN or neuropsychiatric systemic lupus erythematosus (NPSLE) with patients without these symptoms. The expression of TLR mRNA was determined by RT‒qPCR using a high-throughput SmartChip Real-Time-qPCR system (WaferGen). Multivariate analysis and nonparametric statistics were used for data analysis to assess the associations between TLRs and disease activity and severity. RESULTS: TLR4 (0.044 vs. 0.081, p = 0.012) was upregulated and TLR10 (0.009 vs. 0.006, p = 0.0007) was downregulated in the whole cohort of SLE patients compared to healthy controls. A comparison of the active LN group with participants without kidney involvement revealed increased expression of TLR2 (0.078 vs. 0.03, p = 0.009), and TLR5 (0.035 vs. 0.017, p = 0.03). Moreover, a significant difference was observed in TLR9 expression between inactive LN and the control group (0.014 vs. 0.009, p = 0.01), together with borderline correlation in TLR2 expression (0.04 vs. 0.03, p = 0.06). Receiver operating characteristic (ROC) curve analysis revealed that TLR1 and TLR2 expression were the best potential diagnostic markers for active LN. The NPSLE group showed upregulation of TLR1 (0.088 vs. 0.048, p = 0.01), TLR4 (0.173 vs. 0.066, p = 0.0003) and TLR6 (0.087 vs. 0.036, 0.007). Our correlation analysis supported the close relationships among the expression of individual TLRs in the whole lupus cohort and its subgroups. CONCLUSION: Our study revealed differences in TLR expression between a lupus cohort and healthy controls. Additionally, our analysis provides insight into specific TLR expression in cases with severe organ manifestations, such as LN and NPSLE. The multiple mutual relationships of TLRs demonstrate the activation of innate immunity in SLE and suggest promising targets for future therapies or diagnostics.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nefritida při lupus erythematodes * genetika   krev   MeSH
• systémový lupus erythematodes krev   genetika   MeSH
• toll-like receptory * genetika   biosyntéza   MeSH
• vaskulitida centrálního nervového systému při lupus erythematodes * krev   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection is not limited to the respiratory tract as receptors, including the angiotensin-converting enzyme 2 (ACE2), are expressed across many tissues. This study employed a new conditional mouse model, Rosa26creERT2/chACE2, which expresses human ACE2 (hACE2) across multiple organs, to investigate the effects of SARS-CoV-2 infection beyond the respiratory system. This strain demonstrated susceptibility to SARS-CoV-2 infection in a dose and sex-dependent manner, showing that infected male mice exhibited more severe disease outcomes, including significant weight loss, pronounced lung pathology and dysfunction, and increased mortality, compared to females. In contrast to intratracheal infection, intranasal virus administration facilitated viral spread to the brain, thereby underscoring the nasal route's role in the pathogenesis of neurological manifestations. Intranasal infection also led to increased innate immune system activation as compared to intratracheal virus administration, even though both routes activated the adaptive immune response. This model provides a valuable tool to study SARS-CoV-2 in individual tissues or use a multisystemic approach, and it also advances possibilities for preclinical evaluation of antiviral therapies and vaccine strategies.

• MeSH
• angiotensin-konvertující enzym 2 * genetika   metabolismus   MeSH
• COVID-19 * patologie   virologie   imunologie   genetika   MeSH
• dýchací soustava virologie   patologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• myši MeSH
• plíce virologie   patologie   MeSH
• přirozená imunita MeSH
• SARS-CoV-2 * patogenita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.

• MeSH
• lidé MeSH
• monocyty metabolismus   imunologie   MeSH
• pohyb buněk MeSH
• serotonin * metabolismus   MeSH
• signální transdukce MeSH
• střevní sliznice * metabolismus   patologie   MeSH
• TNF-alfa metabolismus   MeSH
• zánět metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: This study aimed to investigate the associations between radiographic damage, serum biomarkers, and clinical assessments in Czech patients with hand osteoarthritis (HOA) over a five-year follow-up period. METHODS: The study cohort comprised 129 patients diagnosed with HOA, including 72 patients with an erosive subtype and 57 patients with a non-erosive subtype. Radiographs were evaluated using the Kallman scoring system by two independent readers. Blood samples were analysed for markers of dyslipidaemia, bone metabolism, and inflammation. Clinical assessments focused on symptom severity and functional impairment. We employed generalised additive modelling (GAM) to analyse the associations between the Kallman score, serum biomarkers and clinical outcomes. RESULTS: The Kallman score was consistently higher in the erosive subtype compared to the non-erosive subtype across all time points and demonstrated a positive correlation with age in both groups. We demonstrated significant positive associations between radiographic progression and erythrocyte sedimentation rate across both HOA subtypes. Additionally, positive associations with the number of swollen joints and health assessment questionnaire scores were observed in all HOA patients, particularly in those with non-erosive subtypes. In contrast, markers of dyslipidaemia (e.g. LDL‐c or atherogenic index) were negatively associated with radiographic progression. No biomarker reliably differentiated between the erosive and non-erosive subtypes. CONCLUSIONS: Our longitudinal study revealed a significant association between systemic/local inflammation, dyslipidaemia, functional impairment and structural progression in HOA. However, these findings warrant further validation through additional studies to confirm these associations.

• MeSH
• biologické markery * krev   MeSH
• časové faktory MeSH
• dyslipidemie * krev   diagnostické zobrazování   MeSH
• funkční status MeSH
• klouby ruky * diagnostické zobrazování   MeSH
• krevní sedimentace MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mediátory zánětu krev   MeSH
• osteoartróza * diagnostické zobrazování   krev   MeSH
• posuzování pracovní neschopnosti MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci * MeSH
• radiografie MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• zánět krev   diagnostické zobrazování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH