Change of Transferrin Sialylation Differs between Mild Sepsis and Severe Sepsis and Septic Shock

Abstract

Objective and Design To investigate the association between the severity of sepsis and changes in sialylation of serum proteins we have conducted a single center pilot study. Subjects and Methods Sialylation of transferrin (with enzyme-linked lectin assay-ELLA) and total serum proteins (with colorimetric assay) as well as serum iron and transferrin levels were measured in 27 patients with sepsis through the first eight days of the disease. Results Total serum sialylation increased in the first two days, transferrin sialylation decreased, while serum iron and transferrin fell. Patients who developed severe sepsis had either a small or marked change in transferrin sialylation while in patients with mild sepsis sialylation decreased moderately. Conclusion We hypothesize that the change in transferrin sialylation could be a reflection of the intensity of inflammatory response which is insufficient if under-expressed and detrimental if over-expressed. This new feature is a potential marker of sepsis severity early in the disease.

Changes in IgG and total plasma protein glycomes in acute systemic inflammation

“…Differences in protein glycosylation between patients and controls have been previously reported in different inflammatory disorders36. Our previous studies revealed changes in glycosylation during the early course of sepsis and acute pancreatitis373839 and the same changes were observed after the acute inflammatory response has been induced in the animal model40. However, the design of all previous studies prevented them from identifying very early changes, while in this study we clearly demonstrated very extensive glycosylation changes in the first 24 hours after the onset of inflammation.…”

Differential protein expression in patients with urosepsis

“… 10 ChiarlaC- hypothesized that change in transferring sialylation could reflect the intensity of the inflammatory response, and is insufficient if under-expressed and detrimental when overexpressed. 11 , 12 , 13 In this study, TF showed lower levels in the shock group; the most likely explanation is transferring degradation by neuraminidase. Further studies, including measurement of blood neuraminidase concentrations and activity, are needed to understand the exact role of sialic acid decrease in septic patients.…”

“…Decreased expression of TF is associated with sepsis, and TF is consistently low during sepsis 10 . ChiarlaC- hypothesized that change in transferring sialylation could reflect the intensity of the inflammatory response, and is insufficient if under-expressed and detrimental when overexpressed 11, 12, 13. In this study, TF showed lower levels in the shock group; the most likely explanation is transferring degradation by neuraminidase.…”

Comparative analysis of transferrin and IgG N-glycosylation in two human populations

“…Although the biological meaning of different Tf glycosylation patterns is still not completely understood, early research studies have demonstrated that the absence of Tf glycosylation doesn't affect iron binding or Tf binding to a Tf receptor [40][41][42] , while it was shown that it affects cellular iron uptake in vitro and in vivo 40,42 . However, changes in Tf N-glycome can alter its circulation half-life and affect iron transport 43 , which might be an important element of the response to acute inflammation 44,45 . On the other hand, the function of IgG is recognition of foreign pathogens and activation of an appropriate immune response, so it is conceivable IgG glycosylation correlates more with age than with sex, since it was proposed that it somewhat reflects previous antigen encounters during past infections [46][47][48] .…”