Oncofetal fibronectin as a marker for pregnancy-related indications
Methods and products for the detection of oncofetal fibronectin indicating molecules in samples are provided. Methods for imaging of oncofetal fibronectin are provided. In some methods provided herein, the sample is treated with a reagent and/or contacted with a non-specific binder. Provided are methods for testing subjects to ascertain health and disease status and to assess the risk of developing a disease or condition. Methods for detecting the presence of oncofetal fibronectin indicating molecules by a variety of methods such as immunoassays and mass spectrometry also are provided. Methods and products for detection of oncofetal fibronection for selection of concepti are provided.
1 . A method for assessing whether a subject has an increased likelihood of imminent or preterm delivery, comprising:
detecting an oncofetal fibronectin indicating molecule in a sample from a pregnant subject, wherein:
the sample is selected from among serum, plasma, blood, urine, a body tissue, lavage and cervical vaginal fluid sampled from among cervical canal, cervical os, ectocervix, transition zone on the cervix between squamous and columnar cells, posterior fomix, a portion of the vagina below the posterior fomix, lower third of the vagina, labia, cervical interstitial fluid; and
the presence of the oncofetal fibronectin indicating molecule in the sample indicates that the subject has an increased likelihood of imminent or preterm delivery.
2 . The method of claim 1 , wherein the sample is urine.
3 . The method of claim 1 , wherein the amount of oncofetal fibronectin detected is correlated with the likelihood of imminent or preterm delivery
4 . The method of claim 1 , wherein presence of an amount of oncofetal fibronectin indicating molecule at or above a threshold level indicates that the subject has an increased likelihood of imminent or preterm delivery.
5 . The method of claim 1 , wherein:
the amount of oncofetal fibronectin indicating molecule detected is compared to two or more thresholds; and
the sample is classified according to the highest threshold that is less than or equal to the detected amount of oncofetal fibronectin indicating molecule, whereby classification of oncofetal fibronectin indicating molecule in the sample according to the highest threshold indicates that the subject has an increased likelihood of imminent or preterm delivery.
6 . The method of claim 1 , wherein:
the oncofetal fibronectin indicating molecule is selected from among an oncofetal fibronectin protein or a fragment thereof, a nucleic acid molecule encoding oncofetal fibronectin or a fragment thereof, a nucleic acid molecule complementary to a nucleic acid molecule encoding oncofetal fibronectin or a fragment thereof, an autoantibody for oncofetal fibronectin protein or a fragment thereof and an autoantibody for a nucleic acid molecule encoding oncofetal fibronectin or a fragment thereof.
7 . The method of claim 1 , wherein:
detecting the oncofetal fibronectin indicating molecule further comprises:
contacting the sample with a first oncofetal fibronectin binding partner; and
detecting complexes of the binding partner and oncofetal fibronectin, whereby detection of a complex is indicative of the presence of oncofetal fibronectin indicating molecule in the sample.
8 . The method of claim 6 further comprising contacting a sample from the subject with a non-specific binding compound.
9 . The method of claim 7 , wherein the binding partner is detectably labeled.
10 . The method of claim 1 , wherein:
detecting the oncofetal fibronectin indicating molecule comprises:
contacting the sample with a first fibronectin or oncofetal fibronectin binding partner;
contacting the sample with a second fibronectin or oncofetal fibronectin binding partner, wherein:
the second fibronectin or oncofetal fibronectin binding partner is conjugated to a detectable or bindable moiety, or the second fibronectin or oncofetal fibronectin binding partner is immobilized to a solid support.
11 . The method of claim 7 , wherein the binding partner is detectably labeled.
12 . The method of claim 1 , wherein the oncofetal fibronectin indicating molecule is detected by its molecular weight or the weight of a fragment thereof.
13 . The method of claim 12 , wherein the oncofetal fibronectin indicating molecule is detected by mass spectrometry or gel electrophoresis.
14 . The method of claim 7 , wherein the fibronectin or oncofetal fibronectin binding partner is immobilized on a test strip.
15 . A method for determining whether a subject is a candidate for successful induction of labor, comprising:
determining the amount of an oncofetal fibronectin indicating molecule in a sample from a pregnant subject; wherein
if the amount of oncofetal fibronectin indicating molecule is equal to or above a threshold level, the subject is identified as one likely to have a successful induction.
16 . The method of claim 15 , wherein a subject who has a successful induction is an induction that results in vaginal delivery, shorter time to delivery or fewer administrations of induction or pre-induction agents compared to a subject that does not have a successful induction.
17 . The method of claim 15 , further comprising:
administering to the subject having an amount of oncofetal fibronectin indicating molecule equal to or above the threshold level a dose of an agent or procedure effective to induce labor.
18 . The method of claim 17 , further comprising:
evaluating the effectiveness of induction by determining the amount of an oncofetal fibronectin indicating molecule in a sample from a pregnant subject undergoing an induction procedure; and
if the amount of oncofetal fibronectin indicating molecule is equal to or above threshold level, identifying the subject as one who is likely to have a successful induction.
19 . The method of claim 15 , further comprising:
determining a second indicator of induction outcome for the subject, wherein:
if the amount of oncofetal fibronectin indicating molecule is above threshold level and the second indicator indicates favorable induction outcome, the subject is identified as one for whom induction is likely to be successful.
20 . The method of claim 19 , wherein the second indicator of induction outcome is selected from among measurements or observations of the pregnant subject, a measurement or observation of the fetus(es), and medical history of the pregnant subject.
21 . The method of claim 20 , wherein the second indicator is selected from among cervical length, Bishop score, effacement, parity, cervical dilation, gestational age, body mass index, station, consistency, transvaginal ultrasound, and digital examination.
22 . The method of claim 19 , further comprising:
identifying the subject as one for whom induction is likely to be successful; and
administering an induction agent to the subject or subjecting the subject to a procedure.
23 . The method of claim 15 , wherein the sample is collected with a swab selected from among a polyester swab, a cotton swab and a rayon swab.
24 . The method of claim 15 , wherein the sample is contacted with a non-specific binding compound prior to determining the amount of the oncofetal fibronectin indicating molecule.
25 . The method of claim 15 , wherein the oncofetal fibronectin indicating molecule or a fragment thereof is detected by mass spectrometry or gel electrophoresis.
26 . The method of claim 15 , further comprising contacting the sample with a fibronectin or oncofetal fibronectin binding protein; and
detecting the complexes of the oncofetal fibronectin indicating molecule and the fibronectin or oncofetal fibronectin biding protein, wherein the complex is measured by detecting the fibronectin or oncofetal fibronectin binding partner.
27 . The method of claim 26 , wherein the fibronectin or oncofetal fibronectin binding partner is immobilized on a test strip.
28 . The method of claim 1 , wherein:
determining the amount of oncofetal fibronectin indicating molecule comprises:
contacting the sample with an immunoassay test strip.
29 . The method of claim 28 , wherein the test strip contains:
a mobilizable oncofetal fibronectin binding partner conjugated to a detectable moiety and a fibronectin or oncofetal fibronectin binding partner immobilized to the test strip; and
detecting complexes of the mobilizable binding partner, the oncofetal fibronectin indicating molecule, and the immobilized binding partner, whereby detection of a complex is indicative of the amount of oncofetal fibronectin indicating molecule in the sample.
30 . A method for delivery date prediction, comprising:
measuring an oncofetal fibronectin indicating molecule in a sample from a pregnant subject, wherein:
an amount of oncofetal fibronectin indicating molecule in the sample at or above a threshold level indicates an increased likelihood that the subject will deliver within a particular time period.
31 . The method of claim 30 , wherein:
the particular time period is selected from among 3 weeks or less, 2 weeks or less, 10 days or less, 1 week or less, 6 days or less, 5 days or less, 4 days or less, 3 days or less, 2 days or less, or 1 day or less.
32 . A combination, comprising:
a fibronectin or oncofetal fibronectin binding partner and a parturifacient.
33 . The combination of claim 32 , further comprising a non-specific binding compound.
34 . A kit, comprising the combination of claim 32 and optionally instructions for use of the binding partner and parturifacient for assessing whether a subject has an increased likelihood of imminent or preterm delivery.
35 . A kit, comprising:
a fibronectin or oncofetal fibronectin binding partner,
a parturifacient, and
a system for classifying the sample according to one or more threshold levels.