Assays and methods for the diagnosis of post-streptococcal disorders

Abstract

Provided are methods for diagnosing a disease in a subject with a previous streptococcal infection by determining the presence or absence of one or more autoantibodies in a biological sample from the subject, wherein the one or more autoantibodies recognize an antigen from a protein selected from the group consisting of ELAVL2, ELAVL3, ELAVL4, Nova-1, Nova-2, Cdr1, Cdr2; and Cdr3. The presence of such autoantibodies is indicative of a positive diagnosis for a post-streptococcal disease such as PANDAS, post-GABHS glomerulonephritis, rheumatic fever, autism and Syndenham's chorea.

1 . A method for diagnosing a disease in a subject, said method comprising,
 (a) determining the presence or absence of one or more autoantibodies in a biological sample from the subject with a previous Streptococcal infection, wherein the one or more autoantibodies recognize an antigen from a protein selected from the group consisting of ELAVL2, ELAVL3, ELAVL4, Nova-1, Nova-2, Cdr1, Cdr2, and Cdr3 and   (b) identifying the subject as
 (i) having a disease selected from the group consisting of PANDAS, post-GABHS glomerulonephritis, rheumatic fever, autism and Syndenham's chorea, when the presence of one or more antibodies is detected, or 
 (ii) not having one of said diseases caused by the Streptococcal infection when each of said antibodies is absent. 
   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1  wherein at least one autoantibody is selected from the group consisting of anti-Hu, anti-Ri and anti-Yo. 
     
     
         4 - 7 . (canceled) 
     
     
         8 . The method of  claim 1  wherein the disease is PANDAS. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . A method comprising:
 (a) testing a biological sample from a subject for the presence of a marker of a streptococcal infection; and   (b) testing the biological sample for the presence or absence of one or more autoantibodies that recognize an antigen from a protein selected from the group consisting of ELAVL2, ELAVL3, ELAVL4, Nova-1, Nova-2, Cdr1, Cdr2 and Cdr3.   
     
     
         12 . The method of  claim 11  wherein step (a) comprises determining the presence or absence of one or more anti-streptococcal antibodies. 
     
     
         13 . The method of  claim 12  wherein the one or more anti-streptococcal antibodies are selected from the group consisting of anti-streptolysin O, anti-deoxyribonuclease-B, anti-hyaluronidase, anti-nicotinamide adenine dinucleotidase and anti-streptokinase antibodies. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . The method of  claim 11  wherein at least one autoantibody is selected from the group consisting of anti-Hu, anti-Ri and anti-Yo. 
     
     
         17 - 22 . (canceled) 
     
     
         23 . A method comprising:
 (a) testing a biological sample from a subject for the presence of a marker of a streptococcal infection; and   (b) testing the reactivity of one or more autoantibodies in the sample to neuronal cells wherein the one or more autoantibodies recognize an antigen from a protein selected from the group consisting of ELAVL2, ELAVL3, ELAVL4, Nova-1, Nova-2, Cdr1, Cdr2 and Cdr3.   
     
     
         24 . The method of  claim 23  wherein the reactivity is determined by an indirect immunofluoresence assay. 
     
     
         25 . The method of  claim 23  wherein the reactivity is determined by neurite retraction. 
     
     
         26 . The method of  claim 23  wherein step (a) comprises determining the presence or absence of one or more anti-streptococcal antibodies. 
     
     
         27 . The method of  claim 26  wherein the one or more anti-streptococcal antibodies are selected from the group consisting of anti-streptolysin O, anti-deoxyribonuclease-B, anti-hyaluronidase, anti-nicotinamide adenine dinucleotidase and anti-streptokinase. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 23  wherein the protein is selected from the group consisting of ELAVL2, ELAVL3, and ELAVL4. 
     
     
         30 . The method of  claim 29  wherein at least one autoantibody is anti-Hu. 
     
     
         31 . The method of  claim 23  wherein the protein is selected from the group consisting of Nova-1 and Nova-2. 
     
     
         32 . The method of  claim 31  wherein at least one autoantibody is anti-Ri. 
     
     
         33 . The method of  claim 23  wherein the protein is selected from the group consisting of Cdr1, Cdr2, and Cdr3. 
     
     
         34 . The method of  claim 33  wherein at least one autoantibody is anti-Yo. 
     
     
         35 - 36 . (canceled)