| 1. |
- Boij, Roland, et al.
(författare)
-
Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia
- 2012
-
Ingår i: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY. - : John Wiley and Sons. - 1046-7408 .- 8755-8920. ; 68:3, s. 258-270
-
Tidskriftsartikel (refereegranskat)abstract
- Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.
|
|
| 2. |
- Boij, Roland, et al.
(författare)
-
Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia
- 2015
-
Ingår i: American Journal of Reproductive Immunology. - : WILEY-BLACKWELL. - 1046-7408 .- 1600-0897. ; 74:4, s. 368-378
-
Tidskriftsartikel (refereegranskat)abstract
- Problem A deficiency in regulatory T (Treg) cells causing reduced immune regulatory capacity has been proposed in preeclampsia. Objective Utilizing recent advances in flow cytometry phenotyping, we aimed to assess whether a deficiency of Treg subpopulations occurs in preeclampsia. Method of study Six-color flow cytometry was used for Treg phenotyping in 18 preeclamptic women (one early-onset, one severe and 16 both), 20 women with normal pregnancy, and 20 non-pregnant controls. Results No differences were found in major Treg populations including CD127(low)CD25(+)/CD127(ow)FOXP3(+), resting (FOXP3(dim)CD45RA(+)), and activated (FOXP3(bright)CD45RA(-)) Treg cells, whereas preeclamptic women showed increased CTLA-4(+) and CCR4(+) proportions within resting/activated Treg populations. Corticosteroid treatment prior to blood sampling (n = 10) affected the distribution of Treg populations. Conclusions Although we found no major alterations in circulating Treg frequencies, differences in CTLA-4(+) and CCR4(+) frequencies suggest a migratory defect of Treg cells in preeclampsia. Corticosteroid treatment should be taken into account when evaluating Treg cells.
|
|
| 3. |
- Dzidic, Majda, et al.
(författare)
-
Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development
- 2017
-
Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:3, s. 1017-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Although a reduced gut microbiota diversity and low mucosal total IgA levels in infancy have been associated with allergy development, IgA responses to the gut microbiota have not yet been studied. Objective: We sought to determine the proportions of IgA coating together with the characterization of the dominant bacteria, bound to IgA or not, in infant stool samples in relation to allergy development. Methods: A combination of flow cytometric cell sorting and deep sequencing of the 16S rDNA gene was used to characterize the bacterial recognition patterns by IgA in stool samples collected at 1 and 12 months of age from children staying healthy or having allergic symptoms up to 7 years of age. Results: The children with allergic manifestations, particularly asthma, during childhood had a lower proportion of IgA bound to fecal bacteria at 12months of age compared with healthy children. These alterations cannot be attributed to differences in IgA levels or bacterial load between the 2 groups. Moreover, the bacterial targets of early IgA responses (including coating of the Bacteroides genus), as well as IgA recognition patterns, differed between healthy children and children with allergic manifestations. Altered IgA recognition patterns in children with allergy were observed already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breast-fed children. Conclusion: An aberrant IgAresponsiveness to the gutmicrobiota during infancy precedes asthma and allergy development, possibly indicating an impaired mucosal barrier function in allergic children.
|
|
| 4. |
- Dzidic, Majda, et al.
(författare)
-
Allergy development is associated with consumption of breastmilk with a reduced microbial richness in the first month of life
- 2020
-
Ingår i: Pediatric Allergy and Immunology. - : WILEY. - 0905-6157 .- 1399-3038. ; 31, s. 250-257
-
Tidskriftsartikel (refereegranskat)abstract
- Background Early colonization with a diverse microbiota seems to play a crucial role for appropriate immune maturation during childhood. Breastmilk microbiota is one important source of microbes for the infant, transferred together with maternal IgA antibodies. We previously observed that allergy development during childhood was associated with aberrant IgA responses to the gut microbiota already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breastfed infants. Objective To determine the microbial composition and IgA-coated bacteria in breastmilk in relation to allergy development in children participating in an intervention trial with pre- and post-natal Lactobacillus reuteri supplementation. Methods A combination of flow cytometric cell sorting and 16S rRNA gene sequencing was used to characterize the bacterial recognition patterns by IgA in breastmilk samples collected one month post-partum from 40 mothers whose children did or did not develop allergic and asthmatic symptoms during the first 7 years of age. Results The milk fed to children developing allergic manifestations had significantly lower bacterial richness, when compared to the milk given to children that remained healthy. Probiotic treatment influenced the breastmilk microbiota composition. However, the proportions of IgA-coated bacteria, the total bacterial load and the patterns of IgA-coating were similar in breastmilk between mothers of healthy children and those developing allergies. Conclusion Consumption of breastmilk with a reduced microbial richness in the first month of life may play an important role in allergy development during childhood.
|
|
| 5. |
- Dzidic, Majda, et al.
(författare)
-
Oral microbiome development during childhood: an ecological succession influenced by postnatal factors and associated with tooth decay
- 2018
-
Ingår i: The ISME Journal. - : NATURE PUBLISHING GROUP. - 1751-7362 .- 1751-7370. ; 12:9, s. 2292-2306
-
Tidskriftsartikel (refereegranskat)abstract
- Information on how the oral microbiome develops during early childhood and how external factors influence this ecological process is scarce. We used high-throughput sequencing to characterize bacterial composition in saliva samples collected at 3, 6, 12, 24 months and 7 years of age in 90 longitudinally followed children, for whom clinical, dietary and health data were collected. Bacterial composition patterns changed through time, starting with "early colonizers", including Streptococcus and Veillonella; other bacterial genera such as Neisseria settled after 1 or 2 years of age. Dental caries development was associated with diverging microbial composition through time. Streptococcus cristatus appeared to be associated with increased risk of developing tooth decay and its role as potential biomarker of the disease should be studied with species-specific probes. Infants born by C-section had initially skewed bacterial content compared with vaginally delivered infants, but this was recovered with age. Shorter breastfeeding habits and antibiotic treatment during the first 2 years of age were associated with a distinct bacterial composition at later age. The findings presented describe oral microbiota development as an ecological succession where altered colonization pattern during the first year of life may have long-term consequences for childs oral and systemic health.
|
|
| 6. |
|
|
| 7. |
- Ekman, Anna-Karin, et al.
(författare)
-
Systemically elevated Th1-, Th2- and Th17-associated chemokines in psoriasis vulgaris before and after ultraviolet B treatment
- 2013
-
Ingår i: Acta Dermato-Venereologica. - : Society for Publication of Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 93:5, s. 527-531
-
Tidskriftsartikel (refereegranskat)abstract
- Chemokines may contribute to the systemic inflammation that is linked to the increased risk of co-morbidities in patients with psoriasis. The aim of this study was to investigate circulating chemokines in patients with psoriasis and their relationship to disease severity. Analysis of plasma levels of chemokines in patients with psoriasis before narrowband ultraviolet B (UVB) therapy revealed increased expression of Th1-associated CXCL9 and -10, Th2-associated CCL17 and CCL22, and Th17-associated CCL20. CCL20 correlated with disease severity. UVB therapy reduced skin symptoms, but did not affect the chemokine levels in plasma. Anti-CD3 and anti-CD28-mediated activation of peripheral blood mononuclear cells (PBMCs) caused a higher secretion of Th2 cytokine interleukin (IL)-13 by PBMCs from patients with psoriasis than from healthy controls. The sustained high expression of inflammatory chemokines is a potential link to systemic inflammation in psoriasis. UVB therapy may be a more effective treatment of local rather than systemic inflammation.
|
|
| 8. |
- Kvarnström, Maria, 1971-, et al.
(författare)
-
Effect of cryopreservation on expression of Th1 and Th2 cytokines in blood mononuclear cells from patients with different cytokine profiles, analysed with three common assays: an overall decrease of interleukin-4 : An overall decrease of interleukin-4
- 2004
-
Ingår i: Cryobiology. - : Elsevier BV. - 0011-2240 .- 1090-2392. ; 49:2, s. 157-168
-
Tidskriftsartikel (refereegranskat)abstract
- Studies on cytokine expression in blood cells are commonly performed on cryopreserved cells. Previous studies show that cryopreservation affects cytokine expression, but the findings are not consistent. This may be due to divergent effects of freezing on different cytokines, different stimuli, and different patient groups or to the use of different assays in the studies. This study was designed to investigate the effect of freezing on spontaneous, auto-antigen, allergen, and mitogen induced cytokine secretion from peripheral blood mononuclear cells from several groups of patients expressing different cytokine profiles; multiple sclerosis, atopic children, non-atopic children, and pregnant women. The expression of IFN-γ, IL-4, IL-5, IL-9, IL-10, and IL-13 was analysed with ELISA, ELISPOT and/or real time RT-PCR. Our data provide evidence that the process of cryopreservation and thawing does affect the expression of cytokines, both at the protein and the mRNA level. Moreover, the effect varied among different cytokines, different stimuli, and different patient groups, which partly may be explained by differences in optimal freezing conditions for non-activated and activated cells. An increase of allergen and PHA stimulated IFN-γ secretion in atopic children was found following cryopreservation, but no such increase in auto-antigen induced IFN-γ was seen in MS-patients. The most consistent finding was that expression of IL-4 was generally decreased in spontaneous and auto-antigen/allergen induced expression in cryopreserved cells. In conclusion, this study points out the importance of investigation of the effects of freezing for each cytokine, stimuli and patient group before using frozen cells in studies of in vitro cytokine secretion.
|
|
| 9. |
- Papapavlou Lingehed, Georgia, et al.
(författare)
-
Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy
- 2022
-
Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system. Pregnancy represents a natural modulation of the disease course, where the relapse rate decreases, especially in the 3(rd) trimester, followed by a transient exacerbation after delivery. Although the exact mechanisms behind the pregnancy-induced modulation are yet to be deciphered, it is likely that the immune tolerance established during pregnancy is involved. In this study, we used the highly sensitive and specific proximity extension assay technology to perform protein profiling analysis of 92 inflammation-related proteins in MS patients (n=15) and healthy controls (n=10), longitudinally sampled before, during, and after pregnancy. Differential expression analysis was performed using linear models and p-values were adjusted for false discovery rate due to multiple comparisons. Our findings reveal gradual dynamic changes in plasma proteins that are most prominent during the 3(rd) trimester while reverting post-partum. Thus, this pattern reflects the disease activity of MS during pregnancy. Among the differentially expressed proteins in pregnancy, several proteins with known immunoregulatory properties were upregulated, such as PD-L1, LIF-R, TGF-beta 1, and CCL28. On the other hand, inflammatory chemokines such as CCL8, CCL13, and CXCL5, as well as members of the tumor necrosis factor family, TRANCE and TWEAK, were downregulated. Further in-depth studies will reveal if these proteins can serve as biomarkers in MS and whether they are mechanistically involved in the disease amelioration and worsening. A deeper understanding of the mechanisms involved may identify new treatment strategies mimicking the pregnancy milieu.
|
|
| 10. |
- Permert, Johan, et al.
(författare)
-
Life Science på östgötska : förslag till Life science-satsning i Östergötland.
- 2018
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Östergötland är inte någon traditionell Life Science-nod i Sverige, men beslutade våren 2017 att undersöka möjligheterna att finna en position baserat på erkänd kunskapsbas kring mötet människa – teknik. En förstudie initierades med Region Direktören som beställare och uppdraget innebar att kartlägga, analysera och ge förslag till hur en Life Science-satsning skulle kunna vara genomförbar i Östergötland. Triple Helix-modellen, det vill säga samhandling mellan offentlig sektor, universitet och näringsliv är den anmodade modellen för Life Science-satsningar i Sverige. Den tidigare Life Science-satsningen i Östergötland hade fallit på grund av obalans i styrka hos Triple Helixens ingående parter.Ett lyckat Triple Helix-initiativ i Östergötland, som även fått internationell genomslagskraft är CMIV, där radiologin är världskänt genom samarbetet mellan RÖ, LiU och Sectra. Detta initiativ är ett exempel på Triple Helix-samhandling som gett resultat för alla ingående parter. Runt CMIV kan såväl samhällsnytta som patientnytta och tillväxt tydligt identifieras. Ytterligare ett exempel som lyftes fram i direktivet är utveckling av kliniska beslutsstöd för användning i klinisk verksamhet och vidare forskning på kliniska data.För att få en rik bild av CMIV, och andra initiativ kring Life Science i Östergötland, har arbetsgruppen använt sig av berättarteknik och på djupet studerat fem fall inom Life Science-området. Analys av dessa fall har sedan jämförts med erfarenheter av Life Science från andra regioner och ett förslag till lösning har successivt växt fram i diskussioner med arbetsgruppen och den taktiska styrgruppen. Triple Helix-samhandling är tämligen utmanande i praktiken då de olika aktörerna i vård, forskning- och näringsliv måste samhandla för att uppnå ett gemensamt mål. Berättelserna vittnar om att det krävs vilja, mod och förmåga att korsa såväl ämnes- som organisatoriska gränser. Slutsatsen är därför att det finns behov av att träna denna förmåga, men också att skapa en ”en väg in” där möten kan uppstå för att identifiera, matcha och förfina initiativ som kan lösas med hjälp av Triple Helix-samhandling.Förstudien visar att det finns goda förutsättningar att genomföra en Life Science-satsning i Östergötland. Ett flerfakultetsuniversitet samt ett komplett sjukvårdssystem ger den mylla av kunskap, problem/behov samt kritiska massa som visat sig krävas för den här typen av satsningar. Att begränsa den möjligheten till enbart vidareutveckling av CMIV och byggandet av kliniska beslutsstöd vore dock inte att göra möjligheterna rättvisa. Istället föreslås två interrelaterade verksamheter vars huvuduppdrag är att facilitera och stödja innovation och utveckling inom Life Science-sektorn i Östergötland; Triple Helix-Labb och Triple Helix-Akademi. I Triple Helix-Labbet kan problem/behov och lösningar mötas, matchas och förfinas i en vägledningsprocess som kan leda till såväl ökad patientnytta som ökad tillväxt i Östergötland. I Triple Helix-Akademin stärks förmågan till samhandling i Triple Helix för att överbyggakunskap, förståelse och respekt för de värdesystem som korsas. Genom dessa interorganisatoriska strukturer finns förutsättningar att adressera vårdens problem, samtidigt som dessa kan agera tillväxtmotor i Östergötland. I förstudien identifieras fyra olika växtvägar som kan stimuleras via ovan nämna strukturer.För att få utväxling av ovanstående förslag behöver strukturer med närliggande och överlappande uppdrag ses över och ersättas/integreras i Triple Helix-Labbet. Detta arbete är påbörjat i förstudien, men behöver förfinas i det etableringsuppdrag som är nästa steg för att kraftsamla kring Life Science i Östergötland. En Life Science-satsning är en långsiktig handling och kräver en politisk överenskommelse för att bli hållbar över tid. Därför ses detta som en förutsättning för att starta det etableringsprojekt som föreslås i föreliggande rapport.Den här förstudien handlar om Östergötland. Redan idag finns dock etablerade samarbeten med Sydöstra sjukvårdsregionen men även nationellt och internationellt. Östergötland är därmed en nod i flera större nav, beroende på vilket perspektiv som antas. Nodtänkandet är en av förstudiens viktigaste grundpelare, men samtidigt måste förändringsarbetet starta hos var och en av de ingående parterna i en Life Science-satsning och därmed adresserar förstudien främst samhandling mellan de parter som utgör själva hjärtat i satsningen; RÖ och LiU.Den största risken för att en Life Science-satsning ska fallera även denna gång är att den politiska överenskommelsen uteblir, eller att RÖ och LiU stannar i sina invanda samverkanspositioner, och därmed inte antar samhällsutmaningen om ökad patientnytta och ökad tillväxt.Förstudien beslutades av Regionstyrelsen 2018-11-08.
|
|
