Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis.

Abstract

We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analyzed samples of sepsis-suspected patients (n = 20) and age-spanning healthy controls (n = 12) using flow cytometry-based assays. We measured inflammatory markers from plasma fractions and immunophenotyped freshly isolated unfixed peripheral blood mononucleated cells for leukocyte subset representation and expression of activation markers, including chemokine receptors. We found that besides IL-6 and sCD14, CXCR3 ligands (CXCL9 and CXCL10) separated sepsis-suspected patients from healthy controls. The abundance of CD4+ T cells was significantly reduced in patients, while they displayed substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double-positive T cells. Post hoc subgrouping of patients according to their sepsis diagnosis on discharge identified CXCR3/CCR5 double expression on T cells as a separating characteristic for confirmed cases. This work suggests a potential novel axis of dysregulation affecting CXCR3 and CCR5 in early sepsis.