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.

Description

FIELD OF THE INVENTION[0001]The invention relates to medically useful assays and methods for the diagnosis of post-streptococcal infection complications including PANDAS, post-GABHS glomerulonephritis, rheumatic fever, and Syndenham's choreaBACKGROUND OF THE INVENTION[0002]Pediatric Autoimmune Neuropsychiatric Disorder Associated with group A Streptococcal infection (PANDAS) is characterized by pediatric onset; neuropsychiatric disorders (obsessive compulsive disorder [OCD]) and / or tic disorder; abrupt onset and / or episodic course of symptoms; association with group A hemolytic streptococcal (GABHS) infection; and association with neurological abnormalities (motor hyperactivity or adventitious movements, including choreiform movements or tics). PANDAS is one of a spectrum of post-streptococcal infection complications that include post-GABHS glomerulonephritis, rheumatic fever, and Syndenham's chorea.[0003]According to the National Institute of Mental Health (NIMH), children with PAN...

AI Technical Summary

Benefits of technology

[0015](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.

[0016]In one embodiment of the above aspects, testing a biological sample from a subject for the presence of a marker of a streptococcal infection comprises determining the presence or absence of one or more anti-streptococcal antibodies. As used herein, the terms “antibody,”“antibodies,”“autoantibody,” and “autoantibodies” includes whole antibodies and any antigen binding fragment or a single chain thereof. Thus the term “antibody” includes any protein or peptide containing molecule that comprises at least a portion of an immunoglobulin molecule. The terms “antibody,”“antibodies,”“autoantibody,” and “autoantibodies” also include immunoglobulins of any isotype, fragments of antibodies which retain specific binding to antigen, including, but not limited to, Fab, Fab', F(ab)2, Fv, scFv, dsFv, Fd fragments, dAb, VH, VL, VhH, and V-NAR domains; minibodies, diabodies, triabodies, tetrabodies and kappa bodies; multispecific antibody fragments formed from antibody fragments and one or more isolated. Examples of such include, but are not limited to a complementarity determining region (CDR) of a heavy or light chain or a ligand binding portion thereof, a heavy chain or light chain variable region, a heavy chain or light chain constant region, a framework (FR) region, or any portion thereof. The variable regions of the heavy and light chains of the immunoglobulin molecule contain a binding domain that interacts with an antigen. The constant regions of the antibodies (Abs) may mediate the binding of the immunoglobulin to host tissues. The term “anti-” when used before a protein name, anti-Ri, anti-Yo, and anti-Hu, for example, refers to a monoclonal or polyclonal antibody that binds and / or has an affinity to a particular antigen. For example, “anti-Hu” refers to an antibody that binds to the Hu antigen. The antibodies can be polyclonal, monoclonal, multispecific (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity.

Problems solved by technology

Because the molecular mechanisms underlying the disease are largely unknown, there is no clear diagnostic test for these diseases.