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Monocytic HLA-DR expression differs between bacterial etiologies and is inversely related to C-reactive protein and neutrophil count during the course of bloodstream infection
Örebro University, School of Medical Sciences.
Örebro University, School of Medical Sciences.
Örebro University, School of Medical Sciences.
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
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(English)Manuscript (preprint) (Other academic)
National Category
Family Medicine
Identifiers
URN: urn:nbn:se:oru:diva-57488OAI: oai:DiVA.org:oru-57488DiVA: diva2:1091020
Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2017-04-25Bibliographically approved
In thesis
1. Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis
Open this publication in new window or tab >>Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Monocytic human leukocyte antigen-D related (mHLA-DR) expression determined by flow cytometry has been suggested as a biomarker of sepsisinduced immunosuppression.

In order to facilitate use of HLA-DR in clinical practice, a quantitative real-time PCR technique measuring HLA-DR at the transcription level was developed and evalutated. Levels of HLA-DR mRNA correlated to mHLADR expression and were robustly measured, with high reproducibility, during the course of infection. Dynamics of mHLA-DR expression was studied during the first weeks of bloodstream infection (BSI) and was found to be dependent on the bacterial etiology of BSI. Moreover, mHLA-DR was shown to be inversely related to markers of inflammation. In patients with unfavourable outcome, sustained high C-reactive protein level and high neutrophil count were demonstrated along with low mHLA-DR expression and low lymphocyte count. This supports the theory of sustained inflammation in sepsis-induced immunosuppression. The association between mHLA-DR and bacterial etiology may be linked to the clinical trajectory via differences in ability to cause intractable infection. Staphylococcus aureus was the dominating etiology among cases with unfavourable outcome. With focus on patients with S. aureus BSI, those with complicated S. aureus BSI were found to have lower HLA-DR mRNA expression during the first week than those with uncomplicated S. aureus BSI. If these results can be confirmed in a larger cohort, HLA-DR measurement could possibly become an additional tool for early identification of patients who require further investigation to clear infectious foci and achieve source control.

In conclusion, PCR-based measurement of HLA-DR is a promising method for measurements of the immune state in BSI, but needs further evaluation in the intensive care unit setting to define the predictive and prognostic value for deleterious immunosuppression. The etiology of infection should be taken into consideration in future studies of translational immunology in sepsis.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2017. 97 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 161
Keyword
monocyte HLA-DR, sepsis, immunosuppression, bloodstream infection, HLA-DRA, CIITA, qRT-PCR
National Category
Family Medicine
Identifiers
urn:nbn:se:oru:diva-56125 (URN)978-91-7529-191-8 (ISBN)
Public defence
2017-05-19, Örebro universitet, Campus USÖ, hörsal C3, Södra Grev Rosengatan 32, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-05-24Bibliographically approved

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