Diagnostic biomarker to predict women at risk for preterm delivery

Abstract

The invention relates to biomarkers associated with preterm delivery. More specifically, the invention provides methods of measuring biomarkers including but not limited to cytokines, cytokine receptors, cytokine receptor antagonists, chemokines, chemokine receptors, and/or chemokine receptor antagonists found in women that are at risk for preterm delivery. The diagnostic methods may be performed on whole blood.

What is claimed is: 
     
         1 . A method, comprising:
 obtaining a biological sample from a woman who desires an assessment of her risk for preterm delivery;   exposing the biological sample ex vivo to an antigen and/or a stimulant; and   assessing an immune response to predict whether the woman is at risk for preterm delivery.   
     
     
         2 . The method of  claim 1 , further comprising separating blood cells from the sample and exposing the separated blood cells to the antigen. 
     
     
         3 . The method of  claim 1 , wherein the biological sample is whole blood. 
     
     
         4 . The method of  claim 1 , wherein exposing the biological sample ex vivo to the antigen or the stimulant is by collecting the biological sample into a container coated with the antigen and/or stimulant. 
     
     
         5 . The method of  claim 4 , further comprising removing plasma from the biological sample and assaying the plasma to assess the immune response. 
     
     
         6 . The method of  claim 5 , wherein removing plasma from the biological sample comprises centrifuging the tube comprising the biological sample and harvesting the plasma. 
     
     
         7 . The method of  claim 1 , wherein the antigen and/or stimulant is cortisol, LPS, phytohemagglutinin, a maternal histocompatibility antigen, a paternal histocompatibility antigen, a fetal histocompatibility antigen, a microbial antigen, a cytokine, a phorbol ester, an agent capable of inducing Th1 or Th2 type differentiation of lymphocytes or combination thereof. 
     
     
         8 . The method of  claim 1 , wherein the antigen is LPS. 
     
     
         9 . The method of  claim 1 , wherein assessing the immune response comprises assaying an expression level of a cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, chemokine receptor antagonist, or combinations thereof. 
     
     
         10 . The method of  claim 9 , wherein the cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, chemokine receptor antagonist is selected from the group consisting of IL-10, IL-13, IL-1RA and combinations thereof. 
     
     
         11 . The method of  claim 9 , wherein a higher or lower expression level of the cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, and/or chemokine receptor antagonist compared to a control indicates that the woman is at an increased risk of preterm delivery. 
     
     
         12 . The method of  claim 11 , wherein the higher or lower expression level of the cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, and/or chemokine receptor antagonist is at least one to three times higher or lower compared to the levels of the control. 
     
     
         13 . The method of  claim 11 , wherein the level of the higher or lower expression of the cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, and/or chemokine receptor antagonist is indicative of a low, medium, or high risk of preterm delivery. 
     
     
         14 . The method of  claim 9 , wherein a statistically significantly higher or lower expression of the cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, and/or chemokine receptor antagonist compared to a control indicates that the woman is at an increased risk of preterm delivery. 
     
     
         15 . The method of  claim 1 , wherein the assessing the immune response comprising using a technique selected from the group consisting of enzyme-linked immunosorbent spot (ELISpot), enzyme-linked immunosorbent assay (ELISA), microarray assay, quantitative BCP, Northern blot assay, Southern blot assay, Western blot assay, immunohistochemical assay, binding assay and combinations thereof. 
     
     
         16 . A kit, comprising:
 a container comprising an antigen and/or a stimulant;   instructions to use the container to collect a biological sample from a woman to detect an immune response; and   instructions to determine the risk of preterm delivery of the woman.   
     
     
         17 . The kit of  claim 16 , further comprising a reagent to detect the immune response. 
     
     
         18 . The kit of  claim 16 , further comprising a positive control and/or a negative control. 
     
     
         19 . A method, comprising:
 obtaining a sample of whole blood from a woman who desires an assessment of her risk for preterm delivery;   exposing the sample ex vivo to an antigen and/or a stimulant by collecting the sample into a container coated with the antigen and/or stimulant; and   assessing an immune response to predict whether the woman is at risk for preterm delivery.   
     
     
         20 . The method of  claim 19 , wherein the antigen and/or stimulant is cortisol, LPS, phytohemagglutinin, or combinations thereof. 
     
     
         21 . The method of  claim 19 , wherein assessing the immune response comprises assaying an expression level of a cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, chemokine receptor antagonist, or combinations thereof, wherein a statistically significantly higher or lower expression level of the cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, and/or chemokine receptor antagonist compared to a control indicates that the woman is at an increased risk of preterm delivery. 
     
     
         22 . The method of  claim 21 , wherein the cytokine, cytokine receptor, cytokine receptor antagonist, chemokine, chemokine receptor, chemokine receptor antagonist is selected from the group consisting of IL-10, IL-13, IL-1RA and combinations thereof.