Cd8+t-cell subsets as markers for prediction of delayed fracture healing

Abstract

The present invention relates to a method for diagnosis of delayed bone fracture healing, comprising determining the frequency of a subpopulation of CD8+ cells selected from a first group comprised of CD8+CD57+, CD8+CD28− and CD8+CD28−/CD57+, in a sample obtained from a subject. The present invention further relates to a system and a kit of parts for prediction and resulting options for preventing of delayed bone fracture healing.

1 . A method for prognosis/prediction of delayed bone fracture healing, wherein said method comprises determining the frequency of a subpopulation of CD8+ cells selected from a first group comprised of CD8+CD57+, CD8+CD28− and CD8+CD28−CD57+, in a sample obtained from a subject. 
     
     
         2 . A method according to  claim 1 , wherein said method further comprises determining the frequency of a subpopulation of CD8+ cells selected from a second group comprised of CD8+CD11a++, CD8+CD11a++CD28−, CD8+CD11a++CD57+ and CD8+CD11a++CD28−CD57+ in said sample. 
     
     
         3 . A method according to  claim 1 , wherein the sample is a blood sample. 
     
     
         4 . A method according to  claim 1 , further comprising determining the frequency of a CD8+CD4+ subpopulation of CD3+ cells in said sample. 
     
     
         5 . A method according to  claim 1 , further comprising determining the level of IL-6 in a sample of peripheral blood. 
     
     
         6 . A method according to  claim 1 , further comprising determining of the Calori-Score of said subject. 
     
     
         7 . A method according to  claims 1 , comprising comparing said frequency of a subpopulation of CD8+ cells, said level of IL-6 or said Calori-Score to a standard. 
     
     
         8 . A method according to  claim 1 , wherein a sample exhibiting a twofold higher frequency of CD8+CD4+ cells compared to a standard value determined for a large population of patients with normal fracture healing, is assigned to a group having an elevated probability for delayed fracture healing. 
     
     
         9 . A method according to  claim 1 , wherein a sample exhibiting a frequency of cells being CD11a++, CD28− or CD57+ that is at least 10% higher compared to a standard value determined for a large population of patients with normal fracture healing, is assigned to a group having an elevated probability for delayed fracture healing. 
     
     
         10 . A method according to  claim 1 , wherein
 a sample showing a frequency of at least 30% for cells being CD28− or CD57+ of the CD8+ cells is assigned to a group having an elevated probability for delayed fracture healing,   a sample showing a frequency of at least 65% for cells being CD11a++ of the CD8+ cells is assigned to a group having an elevated probability for delayed fracture healing, and   a sample showing a frequency of at least 5% for cells being CD4+ of the CD3+ cells is assigned to a group having an elevated probability for delayed fracture healing.   
     
     
         11 . A system for diagnosis of delayed bone fracture healing, comprising
 a device for determination the frequency of a cell population or the level of IL-6 in a sample obtained from a subject, and   a programmed microprocessor,   
       wherein 
       said programmed microprocessor is equipped and designated to run a method according one of the above claims. 
     
     
         12 . A system according to  claim 11 , wherein said device is equipped and designated to determine the frequency of said subpopulation. 
     
     
         13 . A kit of parts for diagnosis of delayed bone fracture healing, comprising an anti-CD8-antibody, an anti-CD4-antibody, and an anti-CD11a-antibody, wherein said antibodies are suitable for fluorescence based flow cytometry. 
     
     
         14 . A kit according to  claim 13 , further comprising an anti-CD57 antibody and/or an anti-CD28-antibody.