Increased concentration of the complement split product C5a in acute pyelonephritis during pregnancy

Abstract

Objective. Pregnant women with acute pyelonephritis develop acute respiratory distress syndrome (ARDS) more frequently than non-pregnant women. The reasons for this remain unknown. The complement system is a complex set of selfassembling proteins that have been implicated in the pathophysiology of ARDS and sepsis. The purpose of this study was to determine if activation of the complement system occurs in pregnant women with acute pyelonephritis. Methods. A cross-sectional study was conducted to determine the plasma concentrations of C3a, C4a and C5a (i.e., complement split products) in pregnant patients with acute pyelonephritis (n = 38) and normal pregnant women (n = 38). The complement split products C3a, C4a and C5a were measured using ELISA. Data were analyzed using non-parametric statistics. Results. 1) The median plasma concentration of C5a in pregnant patients with acute pyelonephritis was significantly higher than that in normal pregnant women (p 5 0.001); 2) there was no statistical difference in the median plasma concentration of C3a and C4a between the two groups (p 4 0.05); and 3) concentrations of C3a, C4a and C5a were not different among patients with acute pyelonephritis with and without bacteremia. Conclusions. 1) Pyelonephritis in pregnant women is associated with an increased plasma concentration of C5a, but not C3a and C4a; and 2) an excess of C5a can predispose pregnant women to develop ARDS and multi-organ failure in pyelonephritis. This finding may have clinical implications since blocking C5a improves ARDS in experimental sepsis.

Endocan, a putative endothelial cell marker, is elevated in preeclampsia, decreased in acute pyelonephritis, and unchanged in other obstetrical syndromes

“…Our findings herein are different, as we observed that the median plasma endocan concentration was lower in pregnancies complicated by acute pyelonephritis than in non-pregnant patients. This is a puzzling observation, given that our systematic studies of the behavior of cytokines [230], chemokines [231], complement [232,233] in acute pyelonephritis and preeclampsia suggest that both conditions are associated with a pro-inflammatory state. However, studies of the transcriptome of peripheral blood in patients with preeclampsia [234] and pyelonephritis [235] suggest that the molecular details of the inflammatory response differ.…”

Human Serum Induces Streptococcal C5a Peptidase Expression

“…As a positive control, O90RscpBProm was incubated in THY medium supplemented with 33% human serum. Based on the physiological concentrations of C5a in serum (34), this medium contains approximately 4 ng of C5a per ml. Cultures were grown to stationary phase overnight, and the whole experiment was done in triplicate.…”

The peripheral whole-blood transcriptome of acute pyelonephritis in human pregnancya

“…Of interest, median maternal plasma concentrations of the anti-inflammatory adipokine adiponectin [70] were lower in patients with pyelonephritis than in normal pregnant women. We have also reported the activation of the complement system, a component of the innate immune system, in acute pyelonephritis in pregnancy, as the median plasma concentrations of complement fragment Bb [118] and complement C5a [117] are higher in pregnant patients with acute pyelonephritis than in normal pregnant women. Complement C5a is a potent chemoattractant for neutrophils and can up-regulate the activating IgG Fc receptors and down-regulate the inhibitory IgG Fc receptors on leukocytes, linking the complement system and IgG Fc receptor effector pathways [112].…”

“…The reasons for this increased susceptibility to microbial products remain unknown. However, acute pyelonephritis during pregnancy has been associated with changes in maternal blood concentrations of soluble cluster of differentiation (CD) 30 (an index of Th2 immune response) [61], adipocytokines (retinol binding protein-4 [141], adiponectin [70], visfatin [71], and resistin [72]), T-cell chemokines (C-X-C motif chemokine 10, CXCL-10) [41], complement products (C5a [117]and fragment Bb [118]), protein Z [92], and soluble tumor necrosis factor-related apoptosis inducing ligand (TRAIL) [18]. …”