Proteomic biomarkers that predict the clinical success of rescue cerclage

Weiner, Carl P.; Lee, Keun-Young; Buhimschi, Catalin S.; Christner, Rob; Buhimschi, Irina A.

doi:10.1016/j.ajog.2004.10.588

Cited by 84 publications

(64 citation statements)

References 31 publications

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“…An MR score of 3 or 4 indicates IAI and is highly predictive of imminent preterm delivery (8). There was no overlap between the patients included in the present study and in our prior studies using this methodology (6,8,31).…”

Section: Methodsmentioning

confidence: 45%

“…Peaks composing the MR score were identified by their conspicuous aspect at or in proximity of their known respective masses, 3,377.0 and 3,448.1 Da on the CHCA tracing (corresponding to HNP2 and -1, respectively) and 10,443.8 and 10,834.5 Da (corresponding to Cal-C and Cal-A, respectively) on the SPA tracings as previously described (6,8,31). Briefly, the regions of interest were manually detected using the centroid peak detection tool built into the software.…”

Section: Methodsmentioning

confidence: 99%

“…We previously demonstrated that it is not necessarily the intrauterine infection that causes poor outcomes but rather the resulting intrauterine inflammation which can damage the fetus long before triggering labor (7). Thus, specific and sensitive tests for intrauterine inflammation rather than for bacterial infection may be more important in the search for targeted treatments.Our group recently identified specific AF fingerprints for two of the four recognized pathways leading to preterm delivery (inflammation and hemorrhage) using proteomic technology (SELDI-TOF [surface-enhanced laser desorption-ionization-time-of-flight] mass spectrometry) (6,8,31). The relevant protein peaks of the final proteomic descriptor were extracted using a logical stepwise algorithm, which we named massrestricted (MR) analysis.…”

mentioning

confidence: 99%

“…Our group recently identified specific AF fingerprints for two of the four recognized pathways leading to preterm delivery (inflammation and hemorrhage) using proteomic technology (SELDI-TOF [surface-enhanced laser desorption-ionization-time-of-flight] mass spectrometry) (6,8,31). The relevant protein peaks of the final proteomic descriptor were extracted using a logical stepwise algorithm, which we named massrestricted (MR) analysis.…”

mentioning

confidence: 99%

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Proteomic but Not Enzyme-Linked Immunosorbent Assay Technology Detects Amniotic Fluid Monomeric Calgranulins from Their Complexed Calprotectin Form

Buhimschi

Weiner

et al. 2005

Clin Vaccine Immunol

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Four proteomic biomarkers (human neutrophil peptide 1 [HNP1], HNP2 [defensins], calgranulin C [Cal-C], and Cal-A) characterize the fingerprint of intra-amniotic inflammation (IAI). We compared proteomic technology using surfaced-enhanced laser desorption-ionization-time of flight (SELDI-TOF) mass spectrometry to enzyme-linked immunosorbent assay (ELISA) for detection of these biomarkers. Amniocentesis was performed on 48 women enrolled in two groups: those with intact membranes (n ‫؍‬ 27; gestational age [GA], 26.0 ؎ 0.8 weeks) and those with preterm premature rupture of the membranes (PPROM; n ‫؍‬ 21; GA, 28.4 ؎ 0.9 weeks). Paired abdominal amniotic fluids (aAFs)-vaginal AFs (vAFs) were analyzed in PPROM women. Quantitative aspects of HNP1-3, Cal-C, Cal-A, and calprotectin (a complex of Cal-A with Cal-B) were assessed by ELISA. SELDI-TOF mass spectrometry tracings from 16/48 (33.3%) aAFs and 13/17 (88.2%) vAFs were consistent with IAI (three or four biomarkers present). IAI (by SELDI-TOF mass spectrometry) was associated with increased HNP1-3 and Cal-C measured by ELISA. However, immunoassays detected Cal-A in only 4 of the AFs even though its specific SELDI-TOF mass spectrometry peak was identified in 19/48 AFs. Calprotectin immunoreactivity was decreased in AFs retrieved from women with IAI (P ‫؍‬ 0.01). In conclusion, IAI is associated with increased HNP1-3 levels. In the absence of isoform-specific ELISAs, mass spectrometry remains the only way to discriminate the HNP biomarker isoforms. Monomeric Cal-A is not reliably estimated by specific ELISA as it binds to Cal-B to form the calprotectin complex. Cal-C was reliably measured by SELDI-TOF mass spectrometry or specific ELISA.Premature delivery (PTD; birth before 37 weeks in humans) is a significant public health problem. While complicating 7 to 12% of deliveries, prematurity is associated with 75% of infant mortality and 50% of long-term neurological handicaps, including blindness, deafness, developmental delay, cerebral palsy, and chronic lung disease (4,10,18,22). The etiologies of most preterm births remain unknown (2, 5).Clinically, PTD presents as either preterm labor with intact membranes or with preterm premature rupture of the membranes (PPROM). Several distinct pathophysiological pathways are implicated as triggers for PTD (21): excessive myometrial stretching, decidual hemorrhage, maternal and fetal stress, and inflammation (9). Inflammation may be initiated along various pathways of which infection is but one. Microbial invasion of the amniotic cavity, as evidenced by a positive amniotic fluid (AF) culture, occurs in 10% of the patients with preterm labor and intact membranes and in 38% of the patients with PPROM (25). We previously demonstrated that it is not necessarily the intrauterine infection that causes poor outcomes but rather the resulting intrauterine inflammation which can damage the fetus long before triggering labor (7). Thus, specific and sensitive tests for intrauterine inflammation rather than for bacterial infection may be more ...

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Section: Methodsmentioning

confidence: 45%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Proteomic but Not Enzyme-Linked Immunosorbent Assay Technology Detects Amniotic Fluid Monomeric Calgranulins from Their Complexed Calprotectin Form

Buhimschi

Weiner

et al. 2005

Clin Vaccine Immunol

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“…The presence of 4 protein biomarkers (neutrophil defensins 2 and 1, calgranulins C and A) were highly predictive of PTB, whether inflammation was secondary to infection or bleeding (15). We further found that the interpretation of the MR score is not binary (disease present or disease absent), but rather a gradient progressing from the absence of disease, to minimal, and then severe inflammation.…”

mentioning

confidence: 68%

Proteomic Biomarkers of Intra-amniotic Inflammation: Relationship with Funisitis and Early-onset Sepsis in the Premature Neonate

Buhimschi

Abdel-Razeq

et al. 2007

Pediatr Res

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ABSTRACT:Our goal was to determine the relationship between 4 amniotic fluid (AF) proteomic biomarkers (human neutrophil defensins 2 and 1, calgranulins C and A) characteristic of intra-amniotic inflammation, and funisitis and early-onset sepsis in premature neonates. The mass restricted (MR) score was generated from AF obtained from women in preterm labor (n ϭ 123). The MR score ranged from 0 -4 (none to all biomarkers present). Funisitis was graded histologically and interpreted in relation to the MR scores. Neonates (n ϭ 97) were evaluated for early-onset sepsis. There was significant correlation between the severity of AF inflammation and the presence (53/123) and grades of funisitis (p Ͻ 0.001). Funisitis occurred independently of the amniocentesis-to-delivery interval or status of the membranes and was best predicted by an MR score 3-4 and an earlier gestational age (GA) at delivery. Neonates born to women with an MR score 3-4 had an increased incidence of suspected/confirmed sepsis, even after adjusting for GA at birth. Calgranulin C had the highest association with clinically significant funisitis, while calgranulin A had the strongest association with early-onset sepsis. To conclude, AF proteomic analysis shows that women with MR scores 3-4 are more likely to have histologic funisitis, and deliver neonates with early-onset sepsis. the rate of preterm birth (PTB) has actually increased over the past 20 y (1). More than 500,000 preterm infants were born in the United States in 2004 (1). Interventions to prevent PTB and its consequences for the fetus should predominantly be targeted at the prevention, early recognition and treatment of several risk factors including intra-amniotic inflammation/ infection (2).Robust scientific evidence has confirmed that when intraamniotic inflammation secondary to, or independent of infection is superimposed upon prematurity, the consequences for the neonate can prove devastating (3,4). This association can be explained by an inflammatory cytokine cascade that seems to be, at least partially, of fetal origin (5,6). Indeed, fetal umbilical vein inflammatory cytokine levels, but not maternal serum values, correlate with the presence and severity of the placental histologic inflammation and umbilical cord vasculitis (7).Funisitis is characterized by perivascular infiltrates of inflammatory cells and is considered one of the strongest hallmarks of microbial invasion of the amniotic cavity and fetal inflammatory syndrome (8,9). While there is some debate with regard to the origin of the amniotic fluid (AF) neutrophilic response to infection (10), there is consensus that the fetal inflammatory neutrophilic response originates initially from the umbilical vein and later from the arteries leading to umbilical cord vasculitis and funisitis (11). Funisitis is a well-recognized risk factor for early-onset sepsis in the premature neonate (12,13).We have previously shown that proteomic mapping of the AF reveals a profile, designated as the Mass Restricted (MR) score, that is highly cha...

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The Incompetent Cervix

Owen¹

2007

Management of High‐Risk Pregnancy

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Proteomic biomarkers that predict the clinical success of rescue cerclage

Cited by 84 publications

References 31 publications

Proteomic but Not Enzyme-Linked Immunosorbent Assay Technology Detects Amniotic Fluid Monomeric Calgranulins from Their Complexed Calprotectin Form

Proteomic but Not Enzyme-Linked Immunosorbent Assay Technology Detects Amniotic Fluid Monomeric Calgranulins from Their Complexed Calprotectin Form

Proteomic Biomarkers of Intra-amniotic Inflammation: Relationship with Funisitis and Early-onset Sepsis in the Premature Neonate

The Incompetent Cervix

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