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Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Sweden.
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2013 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, article id R223Article in journal (Refereed) Published
Abstract [en]

Introduction: Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections. However, traditional monitoring of mHLA-DR by flow cytometry has disadvantages due to specific laboratory requirements. An mRNA-based HLA-DR monitoring by polymerase chain reaction (PCR) would improve the clinical usage and facilitate conduction of large multicenter studies. In this study, we evaluated an mRNA-based HLA-DR monitoring by quantitative real-time PCR (qRT-PCR) as an alternative method to traditional flow cytometry.

Methods: Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n = 30).

Results: A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.

Conclusions: Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.

Place, publisher, year, edition, pages
London, United Kingdom: BioMed Central, 2013. Vol. 17, no 5, article id R223
National Category
Medical and Health Sciences Clinical Laboratory Medicine
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-34293DOI: 10.1186/cc13046ISI: 000331540900039PubMedID: 24093602Scopus ID: 2-s2.0-84884967732OAI: oai:DiVA.org:oru-34293DiVA, id: diva2:704775
Note

Funding Agencies:

Nyckelfonden (Örebro, Sweden)

Research committee of Örebro County Council

Available from: 2014-03-13 Created: 2014-03-13 Last updated: 2018-08-29Bibliographically 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. p. 97
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 161
Keywords
monocyte HLA-DR, sepsis, immunosuppression, bloodstream infection, HLA-DRA, CIITA, qRT-PCR
National Category
General Practice
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: 2018-01-13Bibliographically approved

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Cajander, SaraTina, ElisabetSöderquist, BoKällman, Jan

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