Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response
Epidemiological studies have demonstrated that survivors of acute burn trauma are at long-term increased risk of developing a range of morbidities. The mechanisms underlying this increased risk remain unknown. This study aimed to determine whether burn injury leads to sustained immune dysfunction th...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01481/full |
| _version_ | 1818442116421910528 |
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| author | Blair Z. Johnson Sonia McAlister Sonia McAlister Helen M. McGuire Vetrichevvel Palanivelu Andrew Stevenson Peter Richmond Peter Richmond Debra J. Palmer Debra J. Palmer Jessica Metcalfe Jessica Metcalfe Susan L. Prescott Susan L. Prescott Fiona M. Wood Fiona M. Wood Barbara Fazekas de St Groth Matthew D. Linden Mark W. Fear Vanessa S. Fear |
| author_facet | Blair Z. Johnson Sonia McAlister Sonia McAlister Helen M. McGuire Vetrichevvel Palanivelu Andrew Stevenson Peter Richmond Peter Richmond Debra J. Palmer Debra J. Palmer Jessica Metcalfe Jessica Metcalfe Susan L. Prescott Susan L. Prescott Fiona M. Wood Fiona M. Wood Barbara Fazekas de St Groth Matthew D. Linden Mark W. Fear Vanessa S. Fear |
| author_sort | Blair Z. Johnson |
| collection | DOAJ |
| description | Epidemiological studies have demonstrated that survivors of acute burn trauma are at long-term increased risk of developing a range of morbidities. The mechanisms underlying this increased risk remain unknown. This study aimed to determine whether burn injury leads to sustained immune dysfunction that may underpin long-term morbidity. Plasma and peripheral blood mononuclear cells were collected from 36 pediatric burn survivors >3 years after a non-severe burn injury (<10% total body surface area) and from age/sex-matched non-injured controls. Circulating cytokine and vaccine antibody levels were assessed using multiplex immunoassays and cell profiles compared using a panel of 40 metal-conjugated antibodies and mass cytometry. TNF-α (1.31-fold change from controls), IL-2 (1.18-fold), IL-7 (1.63-fold), and IFN-γ (1.18-fold) were all significantly elevated in the burn cohort. Additionally, burn survivors demonstrated diminished antibody responses to the diphtheria, tetanus, and pertussis vaccine antigens. Comparisons between groups using unsupervised clustering identified differences in proportions of clusters within T-cells, B-cells and myeloid cells. Manual gating confirmed increased memory T-regulatory and central memory CD4+ T-cells, with altered expression of T-cell, B-cell, and dendritic cell markers. Conclusions: This study demonstrates a lasting change to the immune profile of pediatric burn survivors, and highlights the need for further research into post-burn immune suppression and regulation. |
| first_indexed | 2024-12-14T18:39:02Z |
| format | Article |
| id | doaj.art-e4417320647246e984d233488fb707ce |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T18:39:02Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e4417320647246e984d233488fb707ce2022-12-21T22:51:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01481554747Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine ResponseBlair Z. Johnson0Sonia McAlister1Sonia McAlister2Helen M. McGuire3Vetrichevvel Palanivelu4Andrew Stevenson5Peter Richmond6Peter Richmond7Debra J. Palmer8Debra J. Palmer9Jessica Metcalfe10Jessica Metcalfe11Susan L. Prescott12Susan L. Prescott13Fiona M. Wood14Fiona M. Wood15Barbara Fazekas de St Groth16Matthew D. Linden17Mark W. Fear18Vanessa S. Fear19School of Biomedical Sciences, The University of Western Australia, Perth, WA, AustraliaSchool of Medicine, The University of Western Australia, Perth, WA, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, AustraliaRamaciotti Facility for Human Systems Biology and the Charles Perkins Centre, Discipline of Pathology, The University of Sydney, Sydney, NSW, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Perth, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Perth, WA, AustraliaSchool of Medicine, The University of Western Australia, Perth, WA, AustraliaWesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, AustraliaSchool of Medicine, The University of Western Australia, Perth, WA, AustraliaCentre for Allergy and Immunology Research, Telethon Kids Institute, Perth, WA, AustraliaSchool of Medicine, The University of Western Australia, Perth, WA, AustraliaCentre for Allergy and Immunology Research, Telethon Kids Institute, Perth, WA, AustraliaSchool of Medicine, The University of Western Australia, Perth, WA, AustraliaCentre for Allergy and Immunology Research, Telethon Kids Institute, Perth, WA, AustraliaSchool of Medicine, The University of Western Australia, Perth, WA, AustraliaDepartment of Health WA, Perth, WA, AustraliaRamaciotti Facility for Human Systems Biology and the Charles Perkins Centre, Discipline of Pathology, The University of Sydney, Sydney, NSW, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Perth, WA, AustraliaSchool of Biomedical Sciences, The University of Western Australia, Perth, WA, AustraliaGenetic and Rare Diseases, Telethon Kids Institute, Perth, WA, AustraliaEpidemiological studies have demonstrated that survivors of acute burn trauma are at long-term increased risk of developing a range of morbidities. The mechanisms underlying this increased risk remain unknown. This study aimed to determine whether burn injury leads to sustained immune dysfunction that may underpin long-term morbidity. Plasma and peripheral blood mononuclear cells were collected from 36 pediatric burn survivors >3 years after a non-severe burn injury (<10% total body surface area) and from age/sex-matched non-injured controls. Circulating cytokine and vaccine antibody levels were assessed using multiplex immunoassays and cell profiles compared using a panel of 40 metal-conjugated antibodies and mass cytometry. TNF-α (1.31-fold change from controls), IL-2 (1.18-fold), IL-7 (1.63-fold), and IFN-γ (1.18-fold) were all significantly elevated in the burn cohort. Additionally, burn survivors demonstrated diminished antibody responses to the diphtheria, tetanus, and pertussis vaccine antigens. Comparisons between groups using unsupervised clustering identified differences in proportions of clusters within T-cells, B-cells and myeloid cells. Manual gating confirmed increased memory T-regulatory and central memory CD4+ T-cells, with altered expression of T-cell, B-cell, and dendritic cell markers. Conclusions: This study demonstrates a lasting change to the immune profile of pediatric burn survivors, and highlights the need for further research into post-burn immune suppression and regulation.https://www.frontiersin.org/article/10.3389/fimmu.2020.01481/fullnon-severe burn injuryimmunityvaccinationmass cytometryacute traumasystemic |
| spellingShingle | Blair Z. Johnson Sonia McAlister Sonia McAlister Helen M. McGuire Vetrichevvel Palanivelu Andrew Stevenson Peter Richmond Peter Richmond Debra J. Palmer Debra J. Palmer Jessica Metcalfe Jessica Metcalfe Susan L. Prescott Susan L. Prescott Fiona M. Wood Fiona M. Wood Barbara Fazekas de St Groth Matthew D. Linden Mark W. Fear Vanessa S. Fear Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response Frontiers in Immunology non-severe burn injury immunity vaccination mass cytometry acute trauma systemic |
| title | Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response |
| title_full | Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response |
| title_fullStr | Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response |
| title_full_unstemmed | Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response |
| title_short | Pediatric Burn Survivors Have Long-Term Immune Dysfunction With Diminished Vaccine Response |
| title_sort | pediatric burn survivors have long term immune dysfunction with diminished vaccine response |
| topic | non-severe burn injury immunity vaccination mass cytometry acute trauma systemic |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01481/full |
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