Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.
- MeSH
- ankylózující spondylitida krev diagnóza imunologie MeSH
- axiální spondyloartritida krev diagnóza MeSH
- biologické markery * krev MeSH
- C-reaktivní protein analýza metabolismus MeSH
- HLA-B27 antigen genetika imunologie MeSH
- idiopatické střevní záněty * krev imunologie diagnóza komplikace MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children.Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children.
- MeSH
- dítě MeSH
- gastrointestinální látky terapeutické užití škodlivé účinky MeSH
- humanizované monoklonální protilátky * škodlivé účinky terapeutické užití MeSH
- idiopatické střevní záněty * farmakoterapie imunologie MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- průřezové studie MeSH
- studie případů a kontrol MeSH
- těhotenství MeSH
- ustekinumab * terapeutické užití škodlivé účinky MeSH
- vakcinace * škodlivé účinky MeSH
- zpožděný efekt prenatální expozice * chemicky indukované imunologie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils-elusive granulocytes that are implicated in a plethora of human pathologies1-5-are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPR inhibition screen and functional assays, we reveal a mechanism by which interleukin-33 (IL-33) and interferon-γ (IFNγ) induce the accumulation of active eosinophils in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of patients with inflammatory bowel disease, and are closely associated with CD4+ T cells. Our findings provide insights into the biology of eosinophils and highlight the crucial contribution of this cell type to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
- MeSH
- analýza genové exprese jednotlivých buněk MeSH
- antigeny CD80 metabolismus MeSH
- eozinofily * klasifikace cytologie imunologie metabolismus MeSH
- idiopatické střevní záněty imunologie MeSH
- imunita * MeSH
- interferon gama MeSH
- interleukin 33 MeSH
- kolitida * imunologie patologie MeSH
- lidé MeSH
- myši MeSH
- proteom MeSH
- střeva * imunologie patologie MeSH
- T-lymfocyty MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- biologická terapie metody škodlivé účinky MeSH
- idiopatické střevní záněty * imunologie klasifikace komplikace MeSH
- lidé MeSH
- nemoci, jimž lze předcházet očkováním * imunologie klasifikace prevence a kontrola MeSH
- vakcinace klasifikace metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
x
x
- MeSH
- adalimumab * farmakologie terapeutické užití MeSH
- biosimilární léčivé přípravky klasifikace terapeutické užití MeSH
- dospělí MeSH
- hidradenitis suppurativa farmakoterapie imunologie MeSH
- idiopatické střevní záněty * diagnóza farmakoterapie imunologie klasifikace MeSH
- inhibitory TNF klasifikace terapeutické užití MeSH
- lidé MeSH
- ulcerózní kolitida farmakoterapie imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Narativní přehledový článek se zabývá tematikou predikace a prevence zánětlivých střevních onemocnění (IBD). Při stále se zvyšující celkové incidenci, nízké přirozené mortalitě a zvyšující se délce dožití lze předpokládat, že prevalence brzy dosáhne 1 %. Vzhledem k nákladům na léčbu tak IBD představují, a do budoucna stále více budou, velký zdravotní problém. Díky pokrokům v porozumění některých mechanizmů při rozvoji IBD se začíná zlepšovat jejich predikce. To otvírá nové pole pro případné terapeutické zásahy ještě v době, kdy se obraz IBD plně nerozvine. Jsou popsány některé zásadní predikční modely a teoreticky je pojednáno o některých již běžících a budoucích možných preventivních programech.
This narrative review summarizes data on prediction and prevention of inflammatory bowel disease (IBD). With increasing incidence, low natural mortality and increasing life expectancy, we can expect IBD that prevalence will soon reach about 1%. This in combination with high therapeutic costs means that IBD represent a significant health problem, which is expected to increase in the near future. The identification of IBD development mechanisms has led to an increasing prediction accuracy. This is opening a new field for therapeutic interventions in early stages of IBD development. We describe some of the essential prediction models and prevention programs that are under way or could be introduced in future.
Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.
- MeSH
- abdominální obezita imunologie metabolismus MeSH
- adipokiny metabolismus MeSH
- idiopatické střevní záněty imunologie metabolismus MeSH
- lidé MeSH
- nitrobřišní tuk imunologie metabolismus MeSH
- tuková tkáň imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Alterations in the gut microbiota composition and diversity seem to play a role in the development of chronic diseases, including inflammatory bowel disease (IBD), leading to gut barrier disruption and induction of proinflammatory immune responses. This opens the door for the use of novel health-promoting bacteria. We selected five Parabacteroides distasonis strains isolated from human adult and neonates gut microbiota. We evaluated in vitro their immunomodulation capacities and their ability to reinforce the gut barrier and characterized in vivo their protective effects in an acute murine model of colitis. The in vitro beneficial activities were highly strain dependent: two strains exhibited a potent anti-inflammatory potential and restored the gut barrier while a third strain reinstated the epithelial barrier. While their survival to in vitro gastric conditions was variable, the levels of P. distasonis DNA were higher in the stools of bacteria-treated animals. The strains that were positively scored in vitro displayed a strong ability to rescue mice from colitis. We further showed that two strains primed dendritic cells to induce regulatory T lymphocytes from naïve CD4+ T cells. This study provides better insights on the functionality of commensal bacteria and crucial clues to design live biotherapeutics able to target inflammatory chronic diseases such as IBD.
- MeSH
- Bacteroidetes genetika imunologie izolace a purifikace MeSH
- Caco-2 buňky MeSH
- DNA bakterií genetika metabolismus MeSH
- dospělí MeSH
- feces mikrobiologie MeSH
- idiopatické střevní záněty imunologie mikrobiologie MeSH
- kolitida chemicky indukované imunologie mikrobiologie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- kyselina trinitrobenzensulfonová škodlivé účinky MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- novorozenec MeSH
- regulační T-lymfocyty imunologie MeSH
- střevní mikroflóra imunologie MeSH
- střevní sliznice imunologie MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- myši MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
