Janus kinase (JAK) inhibitors are effective anti-inflammatory agents for treatment of ulcerative colitis (UC).1 According to drug regulatory agencies and international guidelines, JAK inhibitors should be avoided during pregnancy and lactation.2-4 The existing evidence on safety of JAK inhibitors during pregnancy is scarce and almost exclusively limited to tofacitinib.4-7.
- MeSH
- dospělí MeSH
- fetální krev * chemie MeSH
- inhibitory Janus kinas terapeutické užití MeSH
- komplikace těhotenství farmakoterapie MeSH
- lidé MeSH
- mateřské mléko * chemie MeSH
- novorozenec MeSH
- piperidiny * terapeutické užití MeSH
- pyrimidiny * terapeutické užití MeSH
- těhotenství MeSH
- ulcerózní kolitida farmakoterapie krev MeSH
- výsledek těhotenství * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The aim of this study was to evaluate changes in the relative counts of different leukocyte subsets in peripheral and umbilical cord blood in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of intraamniotic inflammation (IAI) and fetal inflammatory response syndrome (FIRS). METHODS: Fifty-two women with singleton pregnancies complicated by PPROM were included in this study. From samples of peripheral and umbilical cord blood, relative counts of these leukocyte subpopulations were determined using multicolor flow cytometry: granulocytes, monocytes, lymphocytes, T cells and their subpopulations, B cells and their subpopulations, and NK cells and their subpopulations. IAI was defined as increased concentrations of interleukin 6 in the amniotic fluid. Amniotic fluid samples were obtained by transabdominal amniocentesis. RESULTS: Women with IAI had higher relative counts of monocytes (p = 0.04) in peripheral blood. There was an increased relative number of granulocytes (p = 0.003) and a decreased number of lymphocytes (p = 0.0048), helper CD4+ T cells (p = 0.019), NK cells (p = 0.0001) within leukocytes, NK cells within lymphocytes (p = 0.003) and CD16+ NK cells within NK cells (p = 0.005) in umbilical cord blood samples of women with FIRS. However, after adjusting the results for gestational age at sampling, all differences disappeared. CONCLUSIONS: The presence of IAI or FIRS is not accompanied by significant changes in the relative counts of immune cells in peripheral blood or umbilical cord blood in pregnancies complicated by PPROM.
- MeSH
- chorioamnionitida imunologie krev MeSH
- dospělí MeSH
- fetální krev * imunologie cytologie MeSH
- interleukin-6 krev metabolismus MeSH
- leukocyty imunologie MeSH
- lidé MeSH
- plodová voda imunologie metabolismus MeSH
- počet leukocytů MeSH
- předčasný odtok plodové vody * imunologie krev MeSH
- průtoková cytometrie MeSH
- syndrom systémové zánětlivé reakce imunologie krev MeSH
- těhotenství MeSH
- zánět imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The aim of the study was to identify predictive values of the soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio and interleukin (IL)-6, assessed with a clinically available method in a large-volume biochemistry laboratory, in maternal blood, amniotic fluid, and umbilical cord blood for the presence of the placental lesions consistent with maternal vascular malperfusion (MVM) and acute histological chorioamnionitis (HCA), respectively. METHODS: This retrospective study included 92 women with preterm labor with intact membranes (PTL) delivered within 7 days of admission with gestational ages between 22+0 and 34+6 weeks. The sFlt-1/PlGF ratio and IL-6 were assessed in stored samples of maternal serum, amniotic fluid, and umbilical cord serum using Elecsys® sFlt-1, PlGF, and IL-6 immunoassays. RESULTS: Women with MVM had a higher sFlt-1/PlGF ratio in the maternal serum, compared to those without MVM (19.9 vs. 4.6; p < 0.0001), but not in the amniotic fluid or umbilical cord blood. A cut-off value of 8 for the sFlt-1/PlGF ratio in maternal serum was identified as optimal for predicting MVM in patients with PTL. Women with HCA had higher concentrations of IL-6 in maternal serum, compared to those without HCA (11.1 pg/mL vs. 8.4 pg/mL; p = 0.03), amniotic fluid (9,216 pg/mL vs. 1,423 pg/mL; p < 0.0001), and umbilical cord blood (20.7 pg/mL vs. 10.7 pg/mL, p = 0.002). Amniotic-fluid IL-6 showed the highest predictive value. A cut-off value of IL-6 concentration in the amniotic fluid of 5,000 pg/mL was found to be optimal for predicting HCA in PTL. CONCLUSION: Maternal serum sFlt-1/PlGF and amniotic fluid IL-6 concentrations can be used for liquid biopsy to predict placental lesions in women with PTL who deliver within 7 days.
- MeSH
- biologické markery krev MeSH
- chorioamnionitida krev diagnóza MeSH
- dospělí MeSH
- fetální krev metabolismus MeSH
- interleukin-6 * krev MeSH
- lidé MeSH
- placenta metabolismus MeSH
- placentární růstový faktor * krev MeSH
- plodová voda metabolismus MeSH
- předčasná porodní činnost * krev MeSH
- prediktivní hodnota testů * MeSH
- receptor 1 pro vaskulární endoteliální růstový faktor * krev MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Advances in single-cell level analytical techniques, especially cytometric approaches, have led to profound innovation in biomedical research, particularly in the field of clinical immunology. This has resulted in an expansion of high-dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis is thus becoming untenable to handle these challenges. Furthermore, most newly developed computational methods lack flexibility and interoperability, hampering their accessibility and usability. Here, we adapted Seurat, an R package originally developed for single-cell RNA sequencing (scRNA-seq) analysis, for high-dimensional flow cytometric data analysis. Based on a 20-marker antibody panel and analyses of T-cell profiles in both adult blood and cord blood (CB), we showcased the robust capacity of Seurat in flow cytometric data analysis, which was further validated by Spectre, another high-dimensional cytometric data analysis package, and conventional manual analysis. Importantly, we identified a unique CD8+ T-cell population defined as CD8+CD45RA+CD27+CD161+ T cell that was predominantly present in CB. We characterised its IFN-γ-producing and potential cytotoxic properties using flow cytometry experiments and scRNA-seq analysis from a published dataset. Collectively, we identified a unique human CB CD8+CD45RA+CD27+CD161+ T-cell subset and demonstrated that Seurat, a widely used package for scRNA-seq analysis, possesses great potential to be repurposed for cytometric data analysis. This facilitates an unbiased and thorough interpretation of complicated high-dimensional data using a single analytical pipeline and opens a novel avenue for data-driven investigation in clinical immunology.
- MeSH
- analýza jednotlivých buněk metody MeSH
- antigeny CD27 metabolismus imunologie MeSH
- antigeny CD45 * metabolismus imunologie MeSH
- CD8-pozitivní T-lymfocyty * imunologie MeSH
- dospělí MeSH
- fetální krev * imunologie cytologie MeSH
- imunofenotypizace metody MeSH
- lektinové receptory NK-buněk - podrodina B imunologie metabolismus MeSH
- lidé MeSH
- průtoková cytometrie * metody MeSH
- software MeSH
- T-lymfocyty - podskupiny imunologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The immune systems of both the mother and the newborn face significant challenges during birth. Proper immune regulation after birth is essential for the survival of neonates. Numerous studies have demonstrated that the neonatal immune system is relatively immature, particularly in its adaptive arm, placing the primary responsibility for immune surveillance on innate immunity. METHODS: Given the significant role of neutrophils in protecting the neonate after birth, we conducted a study investigating the properties of neutrophils in newborn cord blood using various methodological approaches. RESULTS: Our findings demonstrate the presence of immature low-density neutrophils in the cord blood, which are likely responsible for the observed elevated expression of genes coding for proteins essential to antimicrobial response, including myeloperoxidase, neutrophils elastase, and defensins. DISCUSSION: We propose that these cells function normally and support the protection of newborns early after birth. Furthermore, our results suggest that the mode of delivery might significantly influence the programming of neutrophil function. The presented findings emphasize the importance of distinct neutrophil subpopulations in neonatal immunity and their potential impact on early postnatal health.
- MeSH
- antiinfekční látky * metabolismus MeSH
- fetální krev MeSH
- lidé MeSH
- neutrofily * MeSH
- novorozenec MeSH
- přirozená imunita MeSH
- proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Inflammation is considered a fundamental process accompanying physiological human birth, also playing a role in perinatal pathologies. The goal of the study was to assess the concentrations of inflammatory molecules with respect to the mode of delivery and dynamics of inflammatory molecules in neonatal samples in the first 48-72 hours of life. The concentrations of inflammatory cytokines were measured using the Luminex®xMAP multi-analyte profiling platform in cord blood and peripheral neonatal blood. Study groups included newborns delivered spontaneously (spontaneous group) and via elective caesarean section (elective group). Cord blood concentrations of interleukin 6 (IL-6) and procalcitonin were significantly higher (P < 0.0001) in the spontaneous group compared to the elective group. Neonatal blood concentrations of tumour necrosis factor (TNF) from the elective group were significantly higher com-pared to the spontaneous group (P = 0.0077). The concentrations of procalcitonin and TNF significantly increased within the first 48 to 72 hours following either mode of delivery. IL-6 and IL-18 were significantly higher in neonatal compared to umbilical cord blood in the elective group only, while the increase in the spontaneous group did not reach statistical significance. The concentrations of IL-1α, IL-1β, IL-17A and IL-22 did not show significant differen-ces between the spontaneous and elective groups as well as between umbilical cord and neonatal blood. Our findings show physiological differences in the levels of inflammatory molecules following spontaneous vaginal delivery and elective caesarean section. The results can be used as baseline values for the research of various pathologies in newborns.
- MeSH
- císařský řez * MeSH
- fetální krev MeSH
- interleukin-6 * MeSH
- lidé MeSH
- novorozenec MeSH
- prokalcitonin MeSH
- těhotenství MeSH
- TNF-alfa MeSH
- vedení porodu metody MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Cílem této studie bylo porovnat hodnoty interleukinu-6 v pupečníkové a periferní krvi novorozence. Klinickým cílem bylo zjistit, zda lze vyšetřením krve z pupečníku nahradit brzký postnatální odběr periferní krve. Pacienti a metody: Do studie byli zahrnuti novorozenci (< 35. týden gestace) narození v roce 2016–2018 ve Fakultní nemocnici Olomouc. U těchto novorozenců se zároveň podařilo odebrat dostatečné množství krve z pupečníku. Výsledky: Párový odběr se zdařil u 73 novorozenců. Mezi pupečníkovou a periferní hodnotou interleukinu-6 byl zjištěn významný rozdíl (p < 0,001). Medián prvního měření (pupečníková krev) byl 6,5 ng/l, medián druhého měření (periferní krev) 56 ng/l. Nárůst je téměř desetinásobný. Závěr: Hodnoty interleukinu-6 z pupečníkové krve a z časného postnatálního odběru se podstatně liší. Na tuto skutečnost je nutné myslet při jeho klinickém využití.
Introduction: The aim of this study was to compare interleukin-6 values in umbilical cord and peripheral blood of newborns. The clinical goal was to determine whether the examination of cord blood can replace early postnatal peripheral blood collection. Patients and methods: Study included premature newborns (< 35th week of gestation) born in 2016-2018 at Olomouc University Hospital. At the same time, it was possible to collect a sufficient amount of blood from the umbilical cord in these newborns. Results: Paired sampling was successful in 73 of these newborns. A significant difference (p < 0,001) was found between the umbilical cord and peripheral interleukin-6 values. The median of the first measurement (cord blood) was 6,5 ng/l, the median of the second measurement (peripheral blood) was 56 ng/l. The increase is almost ten times bigger. Conclusion: The difference of values between interleukin-6 from umbilical cord blood and from early postnatal collection are significantly different and it is necessary to keep it in mind during its clinical use.
- MeSH
- fetální krev imunologie MeSH
- interleukin-6 * analýza izolace a purifikace krev MeSH
- krev imunologie MeSH
- lidé MeSH
- novorozenec nedonošený imunologie krev MeSH
- novorozenec MeSH
- novorozenecká sepse diagnóza etiologie imunologie prevence a kontrola MeSH
- prospektivní studie MeSH
- pupečník imunologie krevní zásobení MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- fetální krev * MeSH
- kmenové buňky MeSH
- lidé MeSH
- odběr fetální krve * ekonomika metody trendy MeSH
- terapeutické užití MeSH
- transplantace kmenových buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH