Evaluation of the Activity of Neutrophils and Monocytes in Diabetic Patients With Sepsis, Can Surface Antigens HLA-DR and CD64 Be Useful as Prognostic Factors?

BACKGROUND: Patients with diabetes mellitus (DM) exhibit alterations in their immune response when infected by several types of micro-organisms. The increased susceptibility of diabetics to infections is particularly related to abnormalities in the function of neutrophils such as chemotaxis, adhesion and intracellular killing, leading to increased mortality rates. Aims of the study were to assess the phagocytic activity and the expression of antigens HLA-DR and CD64 of monocytes and neutrophils in diabetics with sepsis and evaluate their significance as prognostic factors. METHODS: This is an observational prospective study conducted in a tertiary medical center, referring to a population of 51 diabetic patients who were treated for sepsis. Samples of whole blood were received from the selected patients and were evaluated for the expression of surface antigens HLA-DR and CD64 on monocytes and neutrophils, and for their phagocytic activity as well. RESULTS: Alterations in the phagocytic activity were found in the diabetic patients who developed sepsis, and these were addressed as an elevation in the expression of CD64 on monocytes (CD64M), and a reduction in the expression of HLA-DR on monocytes (HLA-DRM) at least in the initial phase of the acute infection. A significant elevation was also noticed in the phagocytosis rate of both neutrophils and monocytes on day of admission. Survivors had higher rates of both CD64 and HLA-DR on monocytes when compared to non-survivors. No correlation was found between glycemic control, values of inflammatory markers on admission, phagocytosis rate and the survival of diabetics with sepsis. A reduced expression of CD64O, HLA-DRM and the co-expression of CD64/HLA-DR on monocytes in the initial phase of sepsis and poor glycemic control (hemoglobin A1c (HbA1c) > 8.5) was found. CONCLUSIONS: In the present study of diabetic patients with sepsis the phagocytic activity of neutrophils and monocytes is elevated at the initial phase of an acute infection and only the values of CD64 and HLA-DR on monocytes were significantly related to outcome. Further evaluation of these results with large prospective studies is warranted.

Role of CD64 expression on neutrophils in the diagnosis of sepsis and the prediction of mortality in adult critically ill patients.

Intensive care unit patients who developed systemic inflammatory response syndrome (SIRS) with proven microbial etiology were assigned to the infectious causes (n = 29), while patients with negative cultures and more probable other etiology were assigned to the noninfectious causes (n = 37). Flow cytometry was used to detect the presence of CD64 on neutrophils. The multivariate analysis revealed that KPC-producing Klebsiella pneumoniae rectal colonization and >1.39 mean fluorescence intensity (MFI) of CD64 expression on neutrophils upon day 1 of SIRS were significantly associated with an infectious SIRS. The overall mortality was 29% (19 patients) and was independently associated with Simplified Acute Physiology Score II >44 points and multiple-organ dysfunction syndrome, while appropriate antibiotic treatment was identified as predictor of good prognosis. MFI of CD64 expression on neutrophils showed high sensitivity, specificity, and accuracy in the diagnosis of sepsis but not for the prediction of survival.