Abstract
Objectives
Immune checkpoints play an important role in maintaining the balance of the immune system and in the development of autoimmune diseases. A central checkpoint molecule is the programmed cell death protein 1 (PD-1, CD279) which is typically located on the surface of T cells. Its primary ligand PD-L1 is expressed on antigen presenting cells and on cancer cells. Several variants of PD-L1 exist, among these soluble molecules (sPD-L1) present in serum at low concentrations. sPD-L1 was found elevated in cancer and several other diseases. sPD-L1 in infectious diseases has received relatively little attention so far and is therefore subject of this study.
Methods
sPD-L1 serum levels were determined in 170 patients with viral infections (influenza, varicella, measles, Dengue fever, SARS-CoV2) or bacterial sepsis by ELISA and compared to the levels obtained in 11 healthy controls.
Results
Patients with viral infections and bacterial sepsis generally show significantly higher sPD-L1 serum levels compared to healthy donors, except for varicella samples where results do not reach significance. sPD-L1 is increased in patients with impaired renal function compared to those with normal renal function, and sPD-L1 correlates significantly with serum creatinine. Among sepsis patients with normal renal function, sPD-L1 serum levels are significantly higher in Gram-negative sepsis compared to Gram-positive sepsis. In addition, in sepsis patients with impaired renal function, sPD-L1 correlates positively with ferritin and negatively with transferrin.
Conclusions
sPD-L1 serum levels are significantly elevated in patients with sepsis, influenza, mesasles, Dengue fever or SARS-CoV2. Highest levels are detectable in patients with measles and Dengue fever. Also impaired renal function causes an increase in levels of sPD-L1. As a consequence, renal function has to be taken into account in the interpretation of sPD-L1 levels in patients.
Acknowledgments
The authors acknowledge the technical assistance of Christopher Geiger, Nadine Bickel, Margit Lanthaler and their colleagues of the Central Institute for Medical and Chemical Laboratory Diagnosis, University Hospital, Innsbruck, Austria, as well as of Manuela Bayer, Patrick Mucher and Astrid Radakovics from the MedUni Wien Biobank. Part of this work was performed in the fulfillment of requirements for the thesis of V.F. MedUni Wien Biobank and Biobank Innsbruck are part of the Austrian Biobanking consortium BBMRI.at (funded by the Austrian Federal Ministry for Education, Science and Research). We acknowledge Dr. Inge von Zabern for fruitful discussions on this topic and proofreading of the manuscript.
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Research funding: None declared.
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Author contributions: M.A., L.L., G.H., H.S. and A.G. conceived the study. M.A., L.L., V.F. planned and performed the experiments. M.A., L.L., A.E., A.G., F.R., and H.S. analyzed the data. A.G., G.H., F.R., G.W. R.B-W. and H.S. advised on experimental design and data analysis. F.R., R.B-W., H.B., H.H., contributed important patient samples and material from healthy volunteers. All authors contributed to the discussion of the data. The manuscript was written by M.A. and L.L.; all authors critically revised the manuscript.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: Ethics Committee approval from the Medical University of Innsbruck (1776/2019; 1167/2020; UN3810) and Vienna (518/2011) were obtained.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0232).
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