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Matthiesen, Leif
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Publications (10 of 34) Show all publications
Boij, R., Mjosberg, J., Svensson Arvelund, J., Hjorth, M., Berg, G., Matthiesen, L., . . . Ernerudh, J. (2015). Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia. American Journal of Reproductive Immunology, 74(4), 368-378
Open this publication in new window or tab >>Regulatory T-cell Subpopulations in Severe or Early-onset Preeclampsia
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2015 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 74, no 4, p. 368-378Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2015
Keywords
Early-onset preeclampsia; preeclampsia; pregnancy; regulatory T cells
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-122528 (URN)10.1111/aji.12410 (DOI)000362664200009 ()26118401 (PubMedID)
Note

Funding Agencies|FORSS (Medical Research Council of Southeast Sweden); Futurum, academy for Health and Care Jonkoping County Council, Sweden

Available from: 2015-11-09 Created: 2015-11-06 Last updated: 2017-12-01
Abelius, M. S., Janefjord, C., Ernerudh, J., Berg, G., Matthiesen, L., Duchén, K., . . . Jenmalm, M. (2015). The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity. American Journal of Reproductive Immunology, 73(5), 445-459
Open this publication in new window or tab >>The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity
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2015 (English)In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 73, no 5, p. 445-459Article in journal (Refereed) Published
Abstract [en]

PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.

METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.

RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.

CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
National Category
Clinical Medicine Cell and Molecular Biology Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-114069 (URN)10.1111/aji.12350 (DOI)000352810200007 ()25491384 (PubMedID)
Available from: 2015-02-06 Created: 2015-02-06 Last updated: 2018-01-11
Abelius, M. S., Janefjord, C., Ernerudh, J., Berg, G., Matthiesen, L., Duchén, K., . . . Jenmalm, M. (2014). Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women.
Open this publication in new window or tab >>Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106219 (URN)
Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2015-03-25Bibliographically approved
Abelius, M. S., Lempinen, E., Lindblad, K., Ernerudh, J., Berg, G., Matthiesen, L., . . . Jenmalm, M. (2014). Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy. Pediatric Allergy and Immunology, 25(4), 387-393
Open this publication in new window or tab >>Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy
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2014 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 25, no 4, p. 387-393Article in journal (Refereed) Published
Abstract [en]

Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.

Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.

Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.

Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
Keywords
Allergy; CCL17; CCL22; chemokines; pregnancy; Th2
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106218 (URN)10.1111/pai.12235 (DOI)000338037100013 ()
Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2017-12-05Bibliographically approved
Boij, R., Svensson, J., Nilsson-Ekdahl, K., Sandholm, K., Lindahl, T., Palonek, E., . . . Matthiesen, L. (2012). Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia. AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 68(3), 258-270
Open this publication in new window or tab >>Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia
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2012 (English)In: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 68, no 3, p. 258-270Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley and Sons, 2012
Keywords
preeclampsia, coagulation, inflammation, angiogenesis, chemokines, cytokines and early onset preeclampsia
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81815 (URN)10.1111/j.1600-0897.2012.01158.x (DOI)000307440300012 ()
Note

Funding Agencies|FORSS (Medical Research Council of Southeast Sweden)||Futurum (the Research department of County of Jonkoping)||Swedish Research Council|2007-15809-48800-58|Linneaus University (Sweden)||

Available from: 2012-09-26 Created: 2012-09-24 Last updated: 2016-11-11
Boij, R., Berg, G., Nilsson-Ekdahl, K., Svensson, J., Sandholm, K., Lindahl, T., . . . Jarle, M. (2012). Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 109-109. In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY (pp. 109-109). Elsevier, 94(1)
Open this publication in new window or tab >>Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 109-109
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2012 (English)In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2012, Vol. 94, no 1, p. 109-109Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-78578 (URN)10.1016/j.jri.2012.03.447 (DOI)000304579400201 ()
Available from: 2012-06-15 Created: 2012-06-15 Last updated: 2012-06-15
Matthiesen, L. (2012). Letter: Reply to Do dose-related mechanisms exist for the angiogenic behaviours of heparin derivatives?, Yavuc C, Karahan O. [Letter to the editor]. American Journal of Reproductive Immunology and Microbiology, 68(3), 187-188
Open this publication in new window or tab >>Letter: Reply to Do dose-related mechanisms exist for the angiogenic behaviours of heparin derivatives?, Yavuc C, Karahan O.
2012 (English)In: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 68, no 3, p. 187-188Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
John Wiley and Sons, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81820 (URN)10.1111/j.1600-0897.2012.01168.x (DOI)000307440300002 ()
Available from: 2012-09-26 Created: 2012-09-24 Last updated: 2017-12-07
Abelius, M. S., Ernerudh, J., Berg, G., Matthiesen, L., Nilsson, L. & Jenmalm, M. (2011). High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life. Pediatric Research, 70(5), 495-500
Open this publication in new window or tab >>High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life
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2011 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, no 5, p. 495-500Article in journal (Refereed) Published
Abstract [en]

Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.

Keywords
AD, atopic dermatitis, ARC, allergic rhinoconjunctivitis, CB, cord blood, SPT, skin prick test, Th, T-helper
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74499 (URN)10.1203/PDR.0b013e31822f2411 (DOI)000296121100010 ()21796021 (PubMedID)
Available from: 2012-01-30 Created: 2012-01-30 Last updated: 2017-12-08
Abelius, M., Ernerudh, J., Berg, G., Matthiesen, L., Nilsson, L. J. & Jenmalm, M. (2011). Immunological interactions between mother and child: a characterisation of Th1-and Th2-like chemokines during pregnancy, postpartum and childhood in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 170-171. In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY (pp. 170-171). Elsevier, 90(2)
Open this publication in new window or tab >>Immunological interactions between mother and child: a characterisation of Th1-and Th2-like chemokines during pregnancy, postpartum and childhood in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 170-171
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2011 (English)In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, no 2, p. 170-171Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2011
Keywords
Allergy, Chemokines, CXCL11, CCL17, Fetal programming
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70333 (URN)10.1016/j.jri.2011.06.073 (DOI)000293873500069 ()
Available from: 2011-09-02 Created: 2011-09-02 Last updated: 2011-09-02
Ernerudh, J., Forsberg, A., Straka, E., Johansson, E., Bhai Mehta, R., Svensson, J., . . . Jenmalm, M. (2011). T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-131. In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY (pp. 131-131). Elsevier, 90(2)
Open this publication in new window or tab >>T helper cells and T helper cell plasticity in pregnancy in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 90, issue 2, pp 131-131
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2011 (English)In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2011, Vol. 90, no 2, p. 131-131Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier, 2011
Keywords
Pregnancy, T helper cell, Tolerance
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70334 (URN)10.1016/j.jri.2011.06.003 (DOI)000293873500002 ()
Available from: 2011-09-02 Created: 2011-09-02 Last updated: 2012-03-25
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