Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

Holmström, Emilia; Myntti, Tarja; Sorsa, Timo; Kruit, Heidi; Juhila, Juuso; Paavonen, Jorma; Rahkonen, Leena; Stefanović, Vedran

doi:10.1159/000493207

Cited by 21 publications

(11 citation statements)

References 47 publications

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“…In particular, interleukin (IL)-6, -8, and matrix metalloproteinase (MMP)-8 and -9 in the AF have been shown to be the strongest predictors of intra-amniotic infectious and inflammatory conditions in PPROM. 11 12 13 14 Nevertheless, their measurement in current practice may be of limited use due to their invasiveness (i.e., amniocentesis) and relatively low sensitivity. 13 15 On the other hand, lipopolysaccharide (LPS) binding protein (LBP), pentraxin 3 (PTX3), and resistin are known to be important mediators involved in inflammatory and immunological processes during infection.…”

Section: Introductionmentioning

confidence: 99%

Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes

et al. 2021

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Background We sought to determine whether lipopolysaccharide binding protein (LBP), pentraxin 3, resistin, and insulin-like growth factor binding protein (IGFBP)-3 in plasma and amniotic fluid (AF) can predict microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI in women with preterm premature rupture of membranes (PPROM). Methods This was a retrospective cohort study involving 168 singleton pregnant women with PPROM. AF obtained via amniocentesis was cultured and assayed for interleukin (IL)-6 to define IAI and for IL-8 to compare with AF biomarkers. Plasma samples were collected at the time of amniocentesis, and C-reactive protein (CRP) levels in serum were compared with plasma biomarkers. The stored plasma and AF samples were assayed for LBP, pentraxin 3 (PTX3), resistin, and IGFBP-3 by ELISA. Results Multivariate logistic regression analysis revealed that: 1) elevated plasma and AF levels of LBP were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 2) elevated AF, but not plasma, PTX3, and resistin levels were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 3) decreased IGFBP-3 levels in the plasma were independently associated with only IAI, whereas those in the AF were associated with only microbial-associated IAI. Among the tested biomarkers, AF PTX3 and resistin had the highest predictive performance for MIAC, IAI, and microbial-associated IAI (area under the curves [AUC] = 0.85–0.95), which is similar to the performance of AF IL-8. The AUCs of the plasma LBP and IGFBP-3 were similar to that of serum CRP with respect to IAI. Conclusion Maternal plasma LBP and IGFBP-3 are potential biomarkers for the non-invasive identification of IAI in women with PPROM, with a similar accuracy to the serum CRP level. AF LBP, PTX3, resistin, and IGFBP-3 may be involved in the intra-amniotic inflammatory responses in PPROM complicated by MIAC.

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Section: Introductionmentioning

confidence: 99%

Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes

et al. 2021

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“…Furthermore, they explored the correlation between leukocytes and MMP8 levels in the amniotic fluid and observed a significant correlation between the two, which is consistent with MMP8 (human neutrophil collagenase) being largely produced by neutrophils. Several other studies also noted consistent findings with the most significant elevations of amniotic fluid MMP8 in the setting of MIAC, 28–30 supporting its relationship to CAM‐induced leukocyte recruitment.…”

Section: Resultsmentioning

confidence: 55%

Matrix metalloproteinases in preterm prelabor rupture of membranes in the setting of chorioamnionitis: A scoping review

Nguyen

Aronoff

Eastman

2022

American J Rep Immunol

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Fetal or gestational membranes extend from the placenta to enclose the fetus and amniotic fluid. While the membranes spontaneously rupture at term in normal pregnancies, they can rupture prematurely before the onset of labor, termed preterm prelabor rupture of membranes (PPROM). PPROM can be triggered by bacterial infection or sterile inflammation in the membranes, known as chorioamnionitis (CAM). The membranes derive their tensile strength from a collagen‐rich extracellular matrix (ECM); as such, understanding the enzymes and processes that can degrade the membrane ECM are of paramount importance. Matrix metalloproteinases (MMPs) are a class of enzymes capable of degrading collagen and other components of the ECM, and can be induced by inflammation. We used a scoping review to address the question of how MMP activity is associated with PPROM, particularly their induction due to sterile or nonsterile CAM. We have found that the most studied MMPs in PPROM were MMPs 2, 8, and 9. Additionally, some MMPs are constitutively active, while others are induced by inflammation. Mechanistic studies of the pathways that induce MMP activation are sparse, and this area is ripe for future studies. Targeting MMP activation could be a future strategy to delay or prevent PPROM.

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“…These observations are similar to those reported for other maternal blood biomarkers and may be attributed to the common inherent characteristics of non-specific inflammation biomarkers 12,26,56 . Consequently, the clinical utility of the aforementioned plasma biomarkers alone may be limited in the PPROM setting; thus, whether these newly identified plasma-based biomarkers could contribute to identifying PPROM-associated MIAC/IAI when used in combination with other currently available non-invasive tests (e.g., cervical length and inflammatory cytokines in the cervicovaginal fluid) needs to be addressed in future studies 5,12,57,58 . In addition, considering the significant association between the inflammatory response in circulation and SPTD [59][60][61] , it is highly likely that these two biomarkers may be useful for identifying patients at high risk for infection/ inflammation-associated preterm delivery, which deserves to be the focus of future studies.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of plasma to identify novel biomarkers for intra-amniotic infection and/or inflammation in preterm premature rupture of membranes

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Kim

et al. 2023

Sci Rep

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To identify potential plasma biomarkers associated with microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in women with preterm premature rupture of membranes (PPROM). This retrospective cohort study included 182 singleton pregnant women with PPROM (23–33 weeks) who underwent amniocentesis. Plasma samples; all subjects were chosen from these participants and were analyzed using label-free liquid chromatography-tandem mass spectrometry for proteome profiling using a nested case–control study design (cases with MIAC/IAI vs. non-MIAC/IAI controls [n = 9 each]). Three identified target molecules for MIAC/IAI were further verified by ELISA in the study cohort (n = 182). Shotgun proteomic analysis revealed 17 differentially expressed proteins (P < 0.05) in the plasma of MIAC/IAI cases. In particular, the levels of FCGR3A and haptoglobin, but not LRP1, were found to be increased in the plasma of patients with MIAC, IAI, and both MIAC/IAI compared with those without these conditions. Moreover, these differences remained significant after adjusting for gestational age at sampling. The area under the curves of plasma FCGR3A and haptoglobin ranged within 0.59–0.65 with respect to each of the three outcome measures. Plasma FCGR3A and haptoglobin were identified as potential independent biomarkers for less-invasively detecting MIAC/IAI in women with PPROM.

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Cervical and Amniotic Fluid Matrix Metalloproteinase-8 and Interleukin-6 Concentrations in Preterm Pregnancies with or without Preterm Premature Rupture of Membranes

Cited by 21 publications

References 47 publications

Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes

Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3: Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes

Matrix metalloproteinases in preterm prelabor rupture of membranes in the setting of chorioamnionitis: A scoping review

Proteomic analysis of plasma to identify novel biomarkers for intra-amniotic infection and/or inflammation in preterm premature rupture of membranes

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