Diagnosis of a neurological disease

Abstract

The present invention concerns subject matter connected to or making use of lgLON5, lgLON5 fragments and variants of lgLON5 and lgLON5-fragments. In particular the present invention relates to a use of a polypeptide comprising one or more sequences of IgLON5, an lgLON5-fragment or a variant thereof for the diagnosis of a disease, in vitro methods for diagnosing such a disease, a polypeptide comprising one or more sequences of lgLON5, an lgLON5-fragment or a variant thereof or a nucleic acid encoding said polypeptide for use in the treatment of a disease, a pharmaceutical composition comprising such polypeptide, a method for treating such a disease, an autoantibody binding to IgLON5, an lgLON5-fragment or a variant thereof, a method for isolating such autoantibody, a medical or diagnostic device comprising such autoantibody or such polypeptide and a test kit for the diagnosis of a disease, which test kit comprises such autoantibody and/or such polypeptide.

1 . (canceled) 
     
     
         2 . A polypeptide comprising one or more sequences of IgLON5, an IgLON5-fragment, or a variant thereof or a nucleic acid encoding said polypeptide. 
     
     
         3 . An autoantibody binding to at least one of the polypeptides of  claim 2 . 
     
     
         4 - 16 . (canceled) 
     
     
         17 . The polypeptide of  claim 2 , wherein the sequence of IgLON5 is the sequence according to SEQ ID NO:1, and wherein the sequence of the IgLON5-fragment is a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10. 
     
     
         18 . The autoantibody of  claim 3 , wherein the polypeptide is provided in the form of a cell comprising a nucleic acid encoding the polypeptide or in the form of a tissue comprising the polypeptide. 
     
     
         19 . An in vitro method for diagnosing a disease, comprising the steps of:
 a1) contacting a liquid sample comprising an antibody from a subject with a polypeptide of  claim 2 , or   a2) contacting a tissue sample comprising IgLON5, an IgLON5-fragment, or a variant thereof from a subject with an antibody binding to IgLON5, the IgLON5-fragment, or the variant thereof, and, following steps a1) or a2),   b) detecting formation of a complex comprising the antibody and IgLON5, the IgLON5-fragment, or the variant thereof.   
     
     
         20 . The in vitro method of  claim 19 , comprising step a2), wherein the antibody is an autoantibody binding to IgLON5, the IgLON5-fragment, or the variant thereof. 
     
     
         21 . The in vitro method of  claim 19 , wherein the disease is selected from the group consisting of sleep disorders, neurodegenerative diseases, and hypoventilation. 
     
     
         22 . The in vitro method of  claim 19 , wherein the disease is associated with one or more symptoms selected from the group consisting of parasomnia, stridor, sleep apnea, gait instability, dysarthria, dysphagia, limb ataxia, vocal cord paralysis, choreic movements in the limbs and face, memory and attention deficits, apathy, depressed mood, akathisia, and urinary disturbances. 
     
     
         23 . The in vitro method of  claim 19 , wherein the sequence of IgLON5 is the sequence according to SEQ ID NO:1, and wherein the sequence of the IgLON5-fragment is a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10. 
     
     
         24 . The in vitro method of  claim 19 , comprising step a1), wherein the polypeptide comprising one or more sequences of IgLON5, the IgLON5-fragment, or the variant thereof is provided in the form of a cell comprising a nucleic acid encoding the polypeptide or in the form of a tissue comprising the polypeptide. 
     
     
         25 . A test kit for the diagnosis of a disease, comprising at least one of:
 an autoantibody binding to IgLON5, an IgLON5-fragment, or a variant thereof; or   a polypeptide comprising one or more sequences of IgLON5, an IgLON5-fragment, or a variant thereof.   
     
     
         26 . The test kit of  claim 25 , comprising the polypeptide comprising one or more sequences of IgLON5, the IgLON5-fragment, or the variant thereof, wherein the polypeptide is provided in an immobilized form. 
     
     
         27 . The test kit of  claim 25 , further comprising a means for detecting a complex comprising an antibody and IgLON5, the IgLON5-fragment, or the variant thereof. 
     
     
         28 . The test kit of  claim 25 , wherein the disease is selected from the group consisting of sleep disorders, neurodegenerative diseases, and hypoventilation. 
     
     
         29 . The test kit of  claim 25 , wherein the disease is associated with one or more symptoms selected from the group consisting of parasomnia, stridor, sleep apnea, gait instability, dysarthria, dysphagia, limb ataxia, vocal cord paralysis, choreic movements in the limbs and face, memory and attention deficits, apathy, depressed mood, akathisia, and urinary disturbances. 
     
     
         30 . The test kit of  claim 25 , wherein the sequence of IgLON5 is the sequence according to SEQ ID NO:1, and wherein the sequence of the IgLON5-fragment is a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10. 
     
     
         31 . The test kit of  claim 25 , comprising the polypeptide comprising one or more sequences of IgLON5, the IgLON5-fragment, or the variant thereof, wherein the polypeptide is provided in the form of a cell comprising a nucleic acid encoding the polypeptide or in the form of a tissue comprising the polypeptide. 
     
     
         32 . A method for isolating an autoantibody binding to IgLON5, an IgLON5-fragment, or a variant thereof, the method comprising the steps of:
 a) contacting a sample comprising the autoantibody with a polypeptide of  claim 2 , such that a complex is formed;   b) isolating the complex formed in step a);   c) dissociating the complex isolated in step b); and   d) separating the autoantibody from the polypeptide comprising one or more sequences of IgLON5, the IgLON5-fragment, or the variant thereof.   
     
     
         33 . The method of  claim 32 , wherein the polypeptide comprising one or more sequences of IgLON5, the IgLON5-fragment, or the variant thereof is immobilized. 
     
     
         34 . The method of  claim 32 , wherein the sequence of IgLON5 is the sequence according to SEQ ID NO:1, and wherein the sequence of the IgLON5-fragment is a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10. 
     
     
         35 . The method of  claim 32 , wherein the polypeptide comprising one or more sequences of IgLON5, the IgLON5-fragment, or the variant thereof is provided in the form of a cell comprising a nucleic acid encoding the polypeptide or in the form of a tissue comprising the polypeptide. 
     
     
         36 . A method for treating a disease associated with one or more symptoms selected from the group consisting of parasomnia, stridor, sleep apnea, gait instability, dysarthria, dysphagia, limb ataxia, vocal cord paralysis, choreic movements in the limbs and face, memory and attention deficits, apathy, depressed mood, akathisia, and urinary disturbances in a subject, comprising the steps of:
 a) reducing the concentration of autoantibodies binding to IgLON5, an IgLON5-fragment, or a variant thereof in the subject's blood; and/or   b) administering one or more immunosuppressive pharmaceutical substances to the subject.   
     
     
         37 . The method of  claim 36 , comprising administering the one or more immunosuppressive pharmaceutical substances to the subject, wherein the immunosuppressive pharmaceutical substances are selected from the group consisting of rituximab, prednisone, methylprednisolone, cyclophosphamide, mycophenolatemofetil, intravenous immunoglobulin, tacrolimus, cyclosporine, methotrexate, azathioprine, and/or a polypeptide comprising one or more sequences of IgLON5, an IgLON5-fragment, or a variant thereof. 
     
     
         38 . The method of  claim 36 , wherein the sequence of IgLON5 is the sequence according to SEQ ID NO:1, and wherein the sequence of the IgLON5-fragment is a sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:10. 
     
     
         39 . A method of detecting the presence or absence of autoantibodies in a subject, comprising:
 obtaining a sample from a subject;   contacting the sample with a polypeptide comprising one or more sequences of IgLON5, an IgLON5-fragment, or a variant thereof; and   detecting in the sample the presence or absence of at least one complex comprising the polypeptide and an autoantibody binding to the polypeptide.   
     
     
         40 . The method of  claim 39 , wherein the polypeptide is tagged, labeled, or immobilized. 
     
     
         41 . A method of diagnosing and/or treating a disease in a subject, the method comprising:
 obtaining a sample from a subject;   contacting the sample with a polypeptide comprising one or more sequences of IgLON5, an IgLON5-fragment, or a variant thereof;   detecting in the sample the presence or absence of at least one complex comprising the polypeptide and an autoantibody binding to the polypeptide; and   diagnosing the subject with a disease selected from the group consisting of sleep disorders, neurodegenerative diseases, and hypoventilation when the presence of the at least one complex is detected.   
     
     
         42 . The method of  claim 41 , further comprising at least one of (i) administering one or more immunosuppressive pharmaceutical substances to the subject, and (ii) reducing the concentration of autoantibodies binding to IgLON5, an IgLON5-fragment, or a variant thereof in the subject.