Methods of preventing immune-mediated abortion by inhibiting a CD28-mediated costimulatory signal

Abstract

Method of inhibiting and diagnosing spontaneous abortion in a subject are provided. The subject methods are based, inter alia, on the administration of an agent that inhibits a costimulatory signal in a T cell such that spontaneous abortion in the subject is inhibited. The subject methods are also based on the levels of adhesion molecules, inflammatory cytokines, and immune cell surface molecules which are altered in spontaneous abortion.

What is claimed is:  
     
         1 . A prognostic method for determining whether a subject is at risk for developing spontaneous abortion comprising detecting the presence or level of mRNA or polypeptide of one ore more of an adhesion molecule, an inflammatory cytokine, or an immune cell surface molecule in a biological sample obtained from said subject, or isolate of said sample, thereby determining whether the subject is at risk for developing spontaneous abortion.  
     
     
         2 . The method of  claim 1 , wherein the adhesion molecule is selected from the group consisting of VCAM-1, P-selectin, and E-selectin.  
     
     
         3 . The method of  claim 1 , wherein the inflammatory cytokine is selected from the group consisting of IL-2, IL-10, IL-12, IL-11, TNFα, IL-1β, TGF, RANTES, IL-6, and IFN-γ.  
     
     
         4 . The method of  claim 1 , wherein the immune cell surface molecule is selected from the group consisting of B7.1 (CD80), B7.2 (CD86), CD4, CD8, GL50, and ICOS).  
     
     
         5 . A diagnostic method for determining whether a subject is suffering from spontaneous abortion comprising detecting the presence or level of mRNA or polypeptide of one or more of an adhesion molecule, an inflammatory cytokine, or an immune cell surface molecule in a biological sample obtained from said subject, or isolate of said sample, thereby determining whether the subject is having a spontaneous abortion.  
     
     
         6 . The method of  claim 5 , wherein the adhesion molecule is selected from the group consisting of VCAM-1, P-selectin, and E-selectin.  
     
     
         7 . The method of  claim 5 , wherein the inflammatory cytokine is selected from the group consisting of IL-2, IL-10, IL-12, IL-11, TNFα, IL-1β, TGF, RANTES, IL-6, and IFNγ.  
     
     
         8 . The method of  claim 5 , wherein the immune cell surface molecule is selected from the group consisting of B7.1 (CD80), B7.2 (CD86), CD4, CD8, GL50, and ICOS).  
     
     
         9 . A method for determining whether a treatment of a subject for a spontaneous abortion is having the desired effect comprising detecting the presence or level of mRNA or polypeptide of one or more of an adhesion molecule, an inflammatory cytokine, or an immune cell surface molecule in a biological sample obtained from said subject, or isolate of said sample, thereby determining whether the treatment is having the desired effect.  
     
     
         10 . The method of  claim 9 , wherein the adhesion molecule is selected from the group consisting of VCAM-1, P-selectin, and E-selectin.  
     
     
         11 . The method of  claim 9 , wherein the inflammatory cytokine is selected from the group consisting of IL-2, IL-10, IL-12, IL-11, TNFα, IL-1β, TGF, RANTES, IL-6, and IFN-γ.  
     
     
         12 . The method of  claim 9 , wherein the immune cell surface molecule is selected from the group consisting of B7.1 (CD80), B7.2 (CD86), CD4, CD8, GL50, and ICOS).  
     
     
         13 . The methods of any of claims  1 ,  5 , or  9 , further comprising comparing the level of mRNA or polypeptide of one or more of an adhesion molecule, an inflammatory cytokine, or an immune cell surface molecule in the biological sample obtained from said subject, or isolate of said sample, to the level of mRNA or polypeptide of one or more of an adhesion molecule, an inflammatory cytokine, or an immune cell surface molecule in an appropriate control.  
     
     
         14 . The methods of any of  claim 1 ,  5 , or  9 , wherein the biological sample is selected from the group consisting of a tissue sample, a cell sample, or a serum sample.  
     
     
         15 . The method of  claim 14 , wherein the tissue sample is selected from the group consisting of a chorionic villus sample and a placental sample.