Fragment Bb in amniotic fluid: evidence for complement activation by the alternative pathway in women with intra-amniotic infection/inflammation

Abstract

Objective Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm), and in the presence of intra-amniotic infection/ inflammation (IAI). Study design This cross-sectional study included patients in the following groups: 1) midtrimester (n=64); 2) term in spontaneous labor (n=70); 3) term not in labor (n=43); 4) spontaneous preterm labor (PTL) who delivered at term (n=76); 5) PTL without IAI who delivered preterm (n=73); 6) PTL with IAI (n=76); 7) prelabor rupture of the membranes (preterm PROM) without IAI (n=71); and 8) preterm PROM with IAI (n=71). Fragment Bb concentration in amniotic fluid was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results 1) Fragment Bb was detected in all AF samples (n=544); 2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 μg/mL, interquartile range (IQR) 1.78-3.22 vs. 1.64 μg/mL, IQR 1.06-3.49; p<0.001]; 3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI who delivered preterm (4.82 μg/mL, IQR 3.32-6.08 vs. 3.67 μg/mL, IQR 2.35-4.57; p<0.001) and than that of women with an episode of PTL who delivered at term (3.21 μg/mL, IQR 2.39-4.16; p<0.001); 4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 μg/mL, IQR 2.58-5.79 vs. 2.79 μg/mL, IQR 2.09-3.89; p<0.001). 5) Among patients at term, the median AF fragment Bb concentration did not differ between women with spontaneous labor and those without labor (term in labor: 2.47 μg/mL, IQR 1.86-3.22; p=0.97). Conclusions 1) Fragment Bb, an activator of the alternative complement pathway, is a physiologic constituent of the amniotic fluid, and its concentration increases with advancing gestational age; 2) Amniotic fluid concentrations of fragment Bb are higher in pregnancies complicated with IAI; and 3) Labor at term is not associated with changes in the amniotic fluid concentrations of fragment Bb. These findings suggest a role for fragment Bb in the host immune response against IAI.

Pentraxin 3 in amniotic fluid: a novel association with intra-amniotic infection and inflammation

“…Thus, it has been proposed that PTX3 participates in the crosstalk between the cellular and humoral arms of the innate immunity in response to microbial invasion by facilitating the activity of the cellular arm of the innate immune response and modulating complement activation [12]. This support the concept of activation of the innate immune system and the complement pathway as part of the inflammatory response to microbial invasion of the AF [33, 147, 160]. …”

Bacteria and endotoxin in meconium-stained amniotic fluid at term: could intra-amniotic infection cause meconium passage?

“…We have previously demonstrated that MIAC or intraamniotic inflammation are associated with high concentrations of cytokines (such as IL-1α and β, TNFα, IL-6, IL-18, IL-16, leukemia-inhibiting factor, IL-10) [74,131,226–233], chemokines (such as IL-8, monocyte chemoattractant protein-1 [MCP-1], CXCL-10 [IP-10], macrophage inflammatory protein-1α [MIP-1α], growth regulated oncogene-α [GRO-α]) [234–239] complement-split products [240,241], phospholipase A2 (Romero R – unpublished observations) and matrix-degrading enzymes (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) [242–248], as well as other components which participate in the regulation of programmed cell death [249–251]. Therefore, in the context of MIAC and intra-amniotic infection, amniotic fluid contains a high concentration of mediators that, when aspirated in utero , could induce lung inflammation.…”

Fragment Bb: evidence for activation of the alternative pathway of the complement system in pregnant women with acute pyelonephritis

“…Consistent with the latter finding, we have recently reported an association between increased amniotic fluid concentration of fragment Bb and intra-amniotic infection in patients with spontaneous preterm labor with intact membranes. [25] We have proposed that these findings represent alternative pathway activation as part of the fetal innate immune response[59,60] to intra-amniotic infection.…”

“…[24] Moreover, increased amniotic fluid concentration of fragment Bb was reported in patients with preterm labor and preterm premature rupture of membranes with intra-amniotic infection/inflammation. [25]…”