Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia

Journal of Clinical Medicine

JesúsF. Bermejo-Martin¹  Raquel Almansa¹  Alicia Ortega²  Ricardo Alonso³  Marta Suescun³  Laura Feced⁴  Ana Ferrando⁴  Rosario Menéndez⁴  Raúl Méndez⁴ 

[1] Centro de Investigación Biomédica En Red-Enfermedades Respiratorias (CibeRes, 58 CB06/06/0028), Instituto de salud Carlos III (ISCIII), Av. de Monforte de Lemos, 5, 28029 Madrid, Spain;Hospital Clínico Universitario de Valladolid, Av. Ramón y Cajal, 3, 47003 Valladolid, Spain;Laboratory Department, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain;Pneumology Department, Hospital Universitario y Politécnico La Fe/Instituto de Investigación Sanitaria (IIS) La Fe, University of Valencia, 46026 Valencia, Spain;

关键词: pneumonia;    transcriptomic signature;    endothelial;   

DOI  :  10.3390/jcm8091404

来源: DOAJ

【 摘 要 】

Rationale: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or without organ dysfunction and to profile endothelial biomarkers such as proendothelin-1 (proET1) and proadrenomedullin (proADM). Methods: A nested study in a prospective cohort in CAP patients was performed. Expression levels of major histocompatibility complex class II DR alpha (HLA-DRA), CD40 ligand (CD40LG), CD3E, CD28, and inducible T-cell costimulator (ICOS) were quantified by using droplet digital polymerase chain reaction and endothelial biomarkers by immunofluorescence. Results: Ninety-four patients were included, 44.7% of whom had organ failure in one or more organs. A significant decrease in the expression of the five genes with increased levels of proadrenomedullin (proADM) and proendothelin-1 (proET1) was found in CAP with organ failure. The depressed expression of HLA-DRA (odds ratio (OR), 2.94), CD40LG (OR, 3.90), and CD28 (OR, 3.48) was independently associated with organ failure after adjustment for age, Charlson score, and severity. Conclusions. CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage. Simultaneous profiling of immunological and endothelial signatures could help in the early identification of organ failure in CAP and in the implementation of personalized treatment.

【 授权许可】

Unknown