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Jenmalm, Maria, ProfessorORCID iD iconorcid.org/0000-0002-2117-5366
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Publications (10 of 133) Show all publications
Humbert, M., Olofsson, A., Wullimann, D., Niessl, J., Hodcroft, E. B., Cai, C., . . . Karlsson, A. C. (2023). Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age. Proceedings of the National Academy of Sciences of the United States of America, 120(12), Article ID e2220320120.
Open this publication in new window or tab >>Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age
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2023 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 120, no 12, article id e2220320120Article in journal (Refereed) Published
Abstract [en]

Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein–Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination. Copyright © 2023 the Author(s).

Place, publisher, year, edition, pages
National Academy of Sciences, 2023
Keywords
ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1; gamma interferon; interleukin 2; tumor necrosis factor; adult; adulthood; aged; Article; CD4+ T lymphocyte; cellular immunity; child; childhood; comorbidity; controlled study; coronavirus disease 2019; cross reaction; female; human; humoral immunity; major clinical study; male; memory T lymphocyte; nonhuman; protein expression; seroconversion; Severe acute respiratory syndrome coronavirus 2; virus nucleocapsid; virus spike
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-200780 (URN)10.1073/pnas.2220320120 (DOI)36917669 (PubMedID)2-s2.0-85150431616 (Scopus ID)
Available from: 2024-02-07 Created: 2024-02-07 Last updated: 2024-02-07
Åkesson, J., Hojjati, S., Hellberg, S., Raffetseder, J., Khademi, M., Rynkowski, R., . . . Gustafsson, M. (2023). Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis. Nature Communications, 14(1), Article ID 6903.
Open this publication in new window or tab >>Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis
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2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 6903Article in journal (Refereed) Published
Abstract [en]

Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression. Lower levels of neurofilament light chain (NfL) in CSF is superior in predicting the absence of disease activity two years after sampling (replication AUC = 0.77) compared to all other tested proteins. Importantly, we also identify a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B and NfL) that predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). The identification of these proteins may help elucidate pathogenetic processes and might aid decisions on treatment strategies for persons with MS.

Place, publisher, year, edition, pages
NATURE PORTFOLIO, 2023
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-199196 (URN)10.1038/s41467-023-42682-9 (DOI)001129872400021 ()37903821 (PubMedID)
Note

Funding: The study was funded by the Swedish Foundation for Strategic Research (SB16-0011 [M.G., J.E.]), the Swedish Brain Foundation, Knut and Alice Wallenberg Foundation, and Margareth AF Ugglas Foundation, Swedish Research Council (2019-04193 [M.G.], 2018-02776 [J.E.], 2020-02700 [F.P.], 2020-00014 [Z.L.P.], 2021-03092 [J.E.]), the Medical Research Council of Southeast Sweden (FORSS-315121 [J.E.]), NEURO Sweden (F2018-0052 [J.E.]), ALF grants, Region Östergötland, the Swedish Foundation for MS Research and the European Union’s Marie Sklodowska-Curie (813863 [J.E.]). The authors would like to acknowledge support of the Clinical biomarker facility at SciLifeLab Sweden for providing assistance in protein analyses.

Available from: 2023-11-16 Created: 2023-11-16 Last updated: 2024-02-22Bibliographically approved
Ahlbeck, L., Ahlberg, E., Björkander, J., Aldén, C., Papapavlou, G., Palmberg, L., . . . Jenmalm, M. (2022). Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen. Clinical and Experimental Allergy, 52(6), 747-759
Open this publication in new window or tab >>Intralymphatic immunotherapy with one or two allergens renders similar clinical response in patients with allergic rhinitis due to birch and grass pollen
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2022 (English)In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 52, no 6, p. 747-759Article in journal (Refereed) Published
Abstract [en]

Introduction

There is a need for a fast, efficient and safe way to induce tolerance in patients with severe allergic rhinitis. Intralymphatic immune therapy has been shown to be effective.

Methods

Patients with severe birch and timothy allergy were randomized and received three doses of 0.1 ml of birch and 5-grass allergen extracts (10,000 SQ units/ml, ALK-Abello), or birch and placebo or 5-grass and placebo by ultrasound-guided injections into inguinal lymph nodes at monthly intervals. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were evaluated before treatment and after each birch and grass pollen season during three subsequent years. Circulating proportions of T helper subsets and allergen-induced cytokine and chemokine production were analysed by flow cytometry and Luminex.

Results

The three groups reported fewer symptoms, lower use of medication and improved quality of life during the birch and grass pollen seasons each year after treatment at an almost similar rate independently of treatment with one or two allergens. Mild local pain was the most common adverse event. IgE levels to birch decreased, whereas birch-induced IL-10 secretion increased in all three groups. IgG4 levels to birch and timothy and skin prick test reactivity remained mainly unchanged. Conjunctival challenge tests with timothy extract showed a higher threshold for allergen. In all three groups, regulatory T cell frequencies were increased 3 years after treatment.

Conclusions

Intralymphatic immunotherapy with one or two allergens in patients with grass and birch pollen allergy was safe, effective and may be associated with bystander immune modulatory responses.

Place, publisher, year, edition, pages
Chichester, United Kingdom: Wiley-Blackwell Publishing Inc., 2022
Keywords
allergy; intralymphatic immunotherapy; hypersensitivity; rhinoconjunctivitis immunotherapy; intralymphatic; allergy
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:liu:diva-184407 (URN)10.1111/cea.14138 (DOI)000776517300001 ()35332591 (PubMedID)2-s2.0-85127382771 (Scopus ID)
Note

Funding Agencies: Region Östergotland; Medical Research Council of Southeast Sweden (FORSS); Th Bergh Foundation; Asthma and Allergy Association

Available from: 2022-04-21 Created: 2022-04-21 Last updated: 2023-11-27Bibliographically approved
Generó, M. M., Spreckels, J., Jenmalm, M. & Abrahamsson, T. (2021). A protocol for characterization of extremely preterm infant gut microbiota in double-blind clinical trials. STAR Protocols, 2(3), Article ID 100652.
Open this publication in new window or tab >>A protocol for characterization of extremely preterm infant gut microbiota in double-blind clinical trials
2021 (English)In: STAR Protocols, ISSN 2666-1667, Vol. 2, no 3, article id 100652Article in journal (Refereed) Published
Abstract [en]

16S rRNA gene sequencing enables microbial community profiling, but recovering fecal DNA from extremely premature infants is challenging. Here, we describe an optimized protocol for fecal DNA isolation, library preparation for 16S rRNA gene sequencing, taxonomy assignation, and statistical analyses. The protocol is complemented with a quantitative PCR for probiotic L. reuteri identification. This protocol describes how to characterize preterm infant gut microbiota and relate it to probiotic supplementation and clinical outcomes. It is customizable for other clinical trials. For complete details on the use and execution of this protocol, please refer to Martí et al. (2021) and Spreckels et al. (2021).

Place, publisher, year, edition, pages
Cambridge, MA, United States: Cell press, 2021
Keywords
Clinical Protocol; Health Sciences; Microbiology; Molecular Biology; Sequencing
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-183530 (URN)10.1016/j.xpro.2021.100652 (DOI)001049298400006 ()34308378 (PubMedID)2-s2.0-85109457709 (Scopus ID)
Note

Funding: the Lions Forskningsfond mot folksjukdomar (Lions LiU-2019-03041), the Swedish Research Council (grant number 921.2014-7060), the Swedish Society for Medical Research, the Swedish Society of Medicine, the Research Council for South-East Sweden, ALF Grants, Region Östergötland, and BioGaia AB, Stockholm, Sweden.

Available from: 2022-03-11 Created: 2022-03-11 Last updated: 2024-01-08Bibliographically approved
Huoman, J., Martinez-Enguita, D., Olsson, E., Ernerudh, J., Nilsson, L., Duchén, K., . . . Jenmalm, M. (2021). Combined prenatal Lactobacillus reuteri and omega-3 supplementation synergistically modulates DNA methylation in neonatal T helper cells. Clinical Epigenetics, 13(1), Article ID 135.
Open this publication in new window or tab >>Combined prenatal Lactobacillus reuteri and omega-3 supplementation synergistically modulates DNA methylation in neonatal T helper cells
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2021 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Clinical Epigenetics, ISSN 1868-7075, Vol. 13, no 1, article id 135Article in journal (Refereed) Published
Abstract [en]

BackgroundEnvironmental exposures may alter DNA methylation patterns of T helper cells. As T helper cells are instrumental for allergy development, changes in methylation patterns may constitute a mechanism of action for allergy preventive interventions. While epigenetic effects of separate perinatal probiotic or omega -3 fatty acid supplementation have been studied previously, the combined treatment has not been assessed. We aimed to investigate epigenome-wide DNA methylation patterns from a sub-group of children in an on-going randomised double-blind placebo-controlled allergy prevention trial using pre- and postnatal combined Lactobacillus reuteri and omega -3 fatty acid treatment. To this end,>866000 CpG sites (MethylationEPIC 850K array) in cord blood CD4+ T cells were examined in samples from all four study arms (double-treatment: n=18, single treatments: probiotics n=16, omega -3 n=15, and double placebo: n=14). Statistical and bioinformatic analyses identified treatment-associated differentially methylated CpGs and genes, which were used to identify putatively treatment-induced network modules. Pathway analyses inferred biological relevance, and comparisons were made to an independent allergy data set.ResultsComparing the active treatments to the double placebo group, most differentially methylated CpGs and genes were hypermethylated, possibly suggesting induction of transcriptional inhibition. The double-treated group showed the largest number of differentially methylated CpGs, of which many were unique, suggesting synergy between interventions. Clusters within the double-treated network module consisted of immune-related pathways, including T cell receptor signalling, and antigen processing and presentation, with similar pathways revealed for the single-treatment modules. CpGs derived from differential methylation and network module analyses were enriched in an independent allergy data set, particularly in the double-treatment group, proposing treatment-induced DNA methylation changes as relevant for allergy development.ConclusionPrenatal L. reuteri and/or omega -3 fatty acid treatment results in hypermethylation and affects immune- and allergy-related pathways in neonatal T helper cells, with potentially synergistic effects between the interventions and relevance for allergic disease. Further studies need to address these findings on a transcriptional level, and whether the results associate to allergy development in the children. Understanding the role of DNA methylation in regulating effects of perinatal probiotic and omega -3 interventions may provide essential knowledge in the development of efficacious allergy preventive strategies.Trial registration ClinicalTrials.gov, ClinicalTrials.gov-ID: NCT01542970. Registered 27th of February 2012-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01542970.

Place, publisher, year, edition, pages
BMC, 2021
Keywords
Allergy prevention; Combined intervention; Cord blood; CD4+T cells; DNA methylation; Lactobacillus reuteri; MethylationEPIC 850K; omega-3 fatty acids; Prenatal; Postnatal
National Category
Psychiatry
Identifiers
urn:nbn:se:liu:diva-180073 (URN)10.1186/s13148-021-01115-4 (DOI)000670704300003 ()34193262 (PubMedID)
Note

Funding Agencies|Linkoping University; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2016-01698, 201900989]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20140321, 20170365]; Cancer and Allergy Foundation; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [FORSS-666771, FORSS-758981]

Available from: 2021-10-08 Created: 2021-10-08 Last updated: 2024-01-28
Svenvik, M., Raffetseder, J., Brudin, L., Lindberg, R., Blomberg, M., Axelsson, D., . . . Nording, M. L. (2021). Plasma oxylipin levels associated with preterm birth in preterm labor✰. Prostaglandins, Leukotrienes and Essential Fatty Acids, 166, Article ID 102251.
Open this publication in new window or tab >>Plasma oxylipin levels associated with preterm birth in preterm labor✰
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2021 (English)In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 166, article id 102251Article in journal (Refereed) Published
Abstract [en]

Introduction

Preterm labor is a common clinical problem in obstetrics. Since the majority of women with preterm labor eventually deliver at full term, biomarkers are needed to more accurately predict who will deliver preterm. Oxylipins, given their importance in inflammation regulation, are highly interesting in this respect since labor is an inflammatory process.

Methods

Eighty women with preterm labor before 34 weeks of gestation were enrolled in a prospective observational multi-center cohort study. Oxylipin levels of 67 analytes in plasma samples were analyzed by liquid chromatography coupled to tandem mass spectrometry.

Results

Twenty-one (26%) of the women delivered before 34 weeks of gestation, and of those women, fourteen delivered within 48 h of admission. Logistic multivariate regression showed that lower levels of 9,10-DiHODE were associated with delivery before 34 weeks of gestation (aOR 0.12 (0.024–0.62)) and within 48 h ((aOR 0.13 (0.019–0.93)). Furthermore, higher levels of 11,12-DiHETrE were associated with delivery before 34 weeks of gestation ((aOR 6.19 (1.17–32.7)) and higher levels of 8-HETE were associated with delivery within 48 h ((aOR 5.01 (1.13–22.14)).

Conclusions

The oxylipin 9,10-DiHODE may be protective in preterm labor, both for delivery after 34 weeks of gestation and for delivery later than 48 h of admission, whereas 11,12-DiHETrE and 8-HETE display the opposite effect. Larger studies are needed to validate these mediators as biomarkers for prediction of preterm birth following preterm labor.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
Preterm labor, Preterm birth, Oxylipins, Eicosanoids, Biomarker, Prediction
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-174827 (URN)10.1016/j.plefa.2021.102251 (DOI)000633428800004 ()33626402 (PubMedID)2-s2.0-85101321594 (Scopus ID)
Note

Medical Research Council of Southeast Sweden (FORSS) [FORSS-931816]; Region Kalmar County; ALF grants; Region Ostergotland

Available from: 2021-04-06 Created: 2021-04-06 Last updated: 2022-01-23Bibliographically approved
Dzidic, M., Mira, A., Artacho, A., Abrahamsson, T., Jenmalm, M. & Carmen Collado, M. (2020). Allergy development is associated with consumption of breastmilk with a reduced microbial richness in the first month of life. Pediatric Allergy and Immunology, 31, 250-257
Open this publication in new window or tab >>Allergy development is associated with consumption of breastmilk with a reduced microbial richness in the first month of life
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2020 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 31, p. 250-257Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
WILEY, 2020
Keywords
allergy; breastmilk; IgA; microbiota; mother-infant transfer
National Category
Pediatrics
Identifiers
urn:nbn:se:liu:diva-162862 (URN)10.1111/pai.13176 (DOI)000501885300001 ()31736150 (PubMedID)
Note

Funding Agencies|Spanish Ministry of Economy and Competitiveness [BIO2015-68711-R]; Swedish Research CouncilSwedish Research Council [2016-01698]; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [20140321, 20170365]; Cancer and Allergy Foundation; European Research Council (ERC)European Research Council (ERC)Estonian Research Council [639226]

Available from: 2020-01-02 Created: 2020-01-02 Last updated: 2021-04-22
Roepke, E. R., Bruno, V., Nedstrand, E., Boij, R., Strid, C. P., Piccione, E., . . . Ernerudh, J. (2020). Author Correction: Low-molecular-weight-heparin increases Th1- and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial. Scientific Reports, 10(1)
Open this publication in new window or tab >>Author Correction: Low-molecular-weight-heparin increases Th1- and Th17-associated chemokine levels during pregnancy in women with unexplained recurrent pregnancy loss: a randomised controlled trial
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1Article in journal (Other academic) Published
Place, publisher, year, edition, pages
Nature Publishing Group, 2020
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:liu:diva-174298 (URN)10.1038/s41598-020-67807-8 (DOI)000546578200015 ()32587333 (PubMedID)2-s2.0-85087047490 (Scopus ID)
Note

Correction to: Scientifc Reports https://doi.org/10.1038/s41598-019-48799-6

Available from: 2021-03-18 Created: 2021-03-18 Last updated: 2023-12-22Bibliographically approved
van der Heiden, M., Bjorkander, S., Qazi, K. R., Bittmann, J., Hell, L., Jenmalm, M., . . . Sverremark-Ekstrom, E. (2020). Characterization of the gamma delta T-cell compartment during infancy reveals clear differences between the early neonatal period and 2 years of age. Immunology and Cell Biology, 98(1), 79-87
Open this publication in new window or tab >>Characterization of the gamma delta T-cell compartment during infancy reveals clear differences between the early neonatal period and 2 years of age
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2020 (English)In: Immunology and Cell Biology, ISSN 0818-9641, E-ISSN 1440-1711, Vol. 98, no 1, p. 79-87Article in journal (Refereed) Published
Abstract [en]

gamma delta T cells are unconventional T cells that function on the border of innate and adaptive immunity. They are suggested to play important roles in neonatal and infant immunity, although their phenotype and function are not fully characterized in early childhood. We aimed to investigate gamma delta T cells in relation to age, prematurity and cytomegalovirus (CMV) infection. Therefore, we used flow cytometry to characterize the gamma delta T-cell compartment in cord blood and peripheral blood cells from 14-day-, 2-year- and 5-year-old children, as well as in peripheral blood samples collected at several time points during the first months of life from extremely premature neonates. gamma delta T cells were phenotypically similar at 2 and 5 years of age, whereas cord blood was divergent and showed close proximity to gamma delta T cells from 14-day-old neonates. Interestingly, 2-year-old children and adults showed comparable V delta 2(+) gamma delta T-cell functionality toward both microbial and polyclonal stimulations. Importantly, extreme preterm birth compromised the frequencies of V delta 1(+) cells and affected the functionality of V delta 2(+) gamma delta T cells shortly after birth. In addition, CMV infection was associated with terminal differentiation of the V delta 1(+) compartment at 2 years of age. Our results show an adult-like functionality of the gamma delta T-cell compartment already at 2 years of age. In addition, we demonstrate an altered gamma delta T-cell phenotype early after birth in extremely premature neonates, something which could possible contribute to the enhanced risk for infections in this vulnerable group of children.

Place, publisher, year, edition, pages
WILEY, 2020
Keywords
childhood immunity; CMV; cord blood; neonatal immunity; prematurity; gamma delta T cells
National Category
Immunology
Identifiers
urn:nbn:se:liu:diva-162732 (URN)10.1111/imcb.12303 (DOI)000499694100001 ()31680329 (PubMedID)
Note

Funding Agencies|Swedish Research CouncilSwedish Research Council [2016-01715_3]; Torsten Soderberg Foundation; Cancer and Allergy Foundation; Swedish Asthma and Allergy Associations Research Foundation; Hesselman Foundation; Golden Jubilee Memorial Foundation; Crownprincess Lovisa/Axel Tielman Foundations; Engkvist Foundations; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Hedlund Foundation

Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2021-04-25
Qazi, K. R., Bach Jensen, G., van der Heiden, M., Bjorkander, S., Holmlund, U., Haileselassie, Y., . . . Abrahamsson, T. (2020). Extremely Preterm Infants Have Significant Alterations in Their Conventional T Cell Compartment during the First Weeks of Life. Journal of Immunology, 204(1), 68-77
Open this publication in new window or tab >>Extremely Preterm Infants Have Significant Alterations in Their Conventional T Cell Compartment during the First Weeks of Life
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2020 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 204, no 1, p. 68-77Article in journal (Refereed) Published
Abstract [en]

Extremely preterm neonates are particularly susceptible to infections, likely because of severely impaired immune function. However, little is known on the composition of the T cell compartment in early life in this vulnerable population. We conducted a comprehensive phenotypic flow cytometry-based longitudinal analysis of the peripheral conventional T cell compartment of human extremely low gestational age neonates (ELGAN) with extremely low birth weight (ELBW; amp;lt;1000 g) participating in a randomized placebo-controlled study of probiotic supplementation. PBMCs from ELGAN/ELBW neonates were collected at day 14, day 28, and postmenstrual week 36. Comparisons were made with full-term 14-d-old neonates. Total CD4(+) and CD8(+) T cell frequencies were markedly lower in the preterm neonates. The reduction was more pronounced among the CD8(+) population, resulting in an increased CD4/CD8 ratio. The preterm infants were also more Th2 skewed than the full-term infants. Although the frequency of regulatory T cells seemed normal in the ELGAN/ELBW preterm neonates, their expression of the homing receptors alpha 4 beta 7, CCR4, and CCR9 was altered. Notably, ELGAN/ELBW infants developing necrotizing enterocolitis before day 14 had higher expression of CCR9 in CD4(+)T cells at day 14. Chorioamnionitis clearly associated with reduced T regulatory cell frequencies and functional characteristics within the preterm group. Finally, probiotic supplementation with Lactobacillus reuteri did not impose any phenotypic changes of the conventional T cell compartment. In conclusion, notable immaturities of the T cell compartment in ELGAN/ELBW neonates may at least partially explain their increased susceptibility to severe immune-mediated morbidities.

Place, publisher, year, edition, pages
AMER ASSOC IMMUNOLOGISTS, 2020
National Category
Immunology
Identifiers
urn:nbn:se:liu:diva-163021 (URN)10.4049/jimmunol.1900941 (DOI)000503179200007 ()31801814 (PubMedID)
Note

Funding Agencies|Swedish Research Council (Medicine)Swedish Research Council [921.2014-7060, 2016-01715_3]; Ekhaga Foundation; Swedish Society of Medicine; Research Council for South-East Sweden; Region Ostergotland [19-00941-FLR]; BioGaia AB; ALF grants

Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2021-04-25
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ORCID iD: ORCID iD iconorcid.org/0000-0002-2117-5366

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