Human leucocyte antigen (HLA-DR) gene expression is reduced in sepsis and correlates with impaired TNFα response: A diagnostic tool for immunosuppression?

• Published in: PloS one 2017-08, Vol.12 (8), p.e0182427-e0182427
• Main Authors: Winkler, Martin Sebastian, Rissiek, Anne, Priefler, Marion, Schwedhelm, Edzard, Robbe, Linda, Bauer, Antonia, Zahrte, Corinne, Zoellner, Christian, Kluge, Stefan, Nierhaus, Axel
• Format: Article
• Language: English
• Subjects: Aged; Anesthesiology; Antigens; Biological effects; Biology and Life Sciences; Biomarkers; Biomarkers - metabolism; Blood; Case-Control Studies; Critical care; Cytokines; Cytometry; Diagnostic software; Diagnostic systems; Direct reduction; Female; Flow cytometry; Gene expression; Histocompatibility antigen HLA; HLA-DR alpha-Chains - metabolism; Humans; Immune response; Immune system; Immune Tolerance - immunology; Immunological tolerance; Immunology; Immunosuppression; Infections; Inflammation; Innate immunity; Intensive care; Intervention; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Male; Medical diagnosis; Medicine; Medicine and Health Sciences; Middle Aged; Monocytes; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Mortality; Patients; Peripheral blood; Polymerase chain reaction; Prospective Studies; Proteins; Research and Analysis Methods; Ribonucleic acid; RNA; Sepsis; Sepsis - diagnosis; Sepsis - drug therapy; Sepsis - immunology; Sepsis - metabolism; Septic shock; Stimulation; Surgery; Surgical instruments; Target groups; Tumor necrosis factor; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182427

Sepsis is defined as a dysregulated immune response to infection. Impaired immune response in sepsis, often described as endotoxin tolerance, is characterized by unresponsiveness of monocytes on lipopolysaccharide (LPS) stimulation to release tumor necrosis factor α (TNFα). Furthermore, decreased monocyte surface protein expression of human leucocyte antigen DR (HLA-DR) is a marker for changes of the innate immune response during sepsis. Quantitative polymerase chain reaction (qPCR) and flow-cytometry (FACS) have been used to measure protein or gene expression of HLA-DR. We aimed to determine whether changes in mRNA expression of HLA-DR are associated with impaired TNFα response in human sepsis. Surface protein together with mRNA expression of HLA-DR were measured by FACS and qPCR in a cohort of 9 sepsis patients and compared to 10 pre-operative control patients in a prospective study. In addition, 20 patients with post-surgical inflammation, 20 patients with sepsis or septic shock were included and TNFα was determined following ex vivo stimulation of whole blood with 500 pg/mL LPS. Total RNA was prepared from whole blood and subjected to qPCR analysis for expression analysis of HLA-DR alpha (HLA-DRA) to correlate TNFα response with HLA-DRA expression. Patients with sepsis presented higher numbers of monocytes in peripheral blood (P