Method for Diagnosing Multiple Sclerosis

Abstract

Disclosed is a method for diagnosing multiple sclerosis and more particularly to a method for diagnosing multiple sclerosis by measuring levels of antibodies to glycans in a biological sample.

1 . A method of diagnosing multiple sclerosis in a subject, the method comprising
 providing a test sample from a subject;   detecting in said test sample at least one antibody selected from the group consisting of an anti-Glc (α) antibody, an anti-Glc (α 1-4) Glc (α) antibody, an anti-Glc (α 1-4) Glc (β) antibody, an anti-Glc (β) antibody, an anti-Gal (β) antibody; an anti-Glc (β 1-4) Glc (β 1-4) Glc (β) antibody, an anti-GlcNAc (β 1-4) GlcNAc (β) antibody, an anti-L-Araf (α) antibody, an anti-L-Rha (α) antibody, an anti-Gal (β 1-3) [GlcNAc (β 1-6)] GalNAc (α)antibody, an anti-Gal (β 1-4) GlcNAc (α)antibody, an anti-Gal (β 1-3) GalNAc (α) antibody, an anti-Gal (β 1-3) GlcNAc (β) antibody, an anti-GlcA (β) antibody, an anti-GlcA (β) antibody, and an anti-Xyl (α) antibody; and   comparing the levels of said at least one antibody in said test sample to the levels of said at least one antibody in a control sample, wherein said control sample is selected from the group consisting of one or more individuals that have multiple sclerosis symptoms and have a known multiple sclerosis status, and one or more individuals that do not show multiple sclerosis symptoms,   thereby diagnosing multiple sclerosis in said subject.   
   
   
       2 . The method of  claim 1 , wherein said method comprises
 detecting an anti-Glc (α) antibody in said test sample; and   comparing the levels of said antibody in said test sample to said control sample.   
   
   
       3 . The method of  claim 1 , wherein said method comprises
 detecting an anti-Glc (α 1-4) Glc (α) antibody in said test sample; and   
   
   
       4 . The method of  claim 1 , wherein said method comprises
 detecting an anti-Glc (α 1-4) Glc (α) antibody and an anti-Glc (α) antibody in said test sample; and   comparing the level of said antibodies in said test sample to said control sample.   
   
   
       5 . The method of  claim 1 , wherein said control sample consists essentially of a population of one or more individuals that have multiple sclerosis symptoms with a known multiple sclerosis status. 
   
   
       6 . The method of  claim 1 , wherein said test sample is a biological fluid. 
   
   
       7 . The method of  claim 6 , wherein said biological fluid is whole blood, serum, plasma, spinal cord fluid, urine, or saliva. 
   
   
       8 . The method of  claim 1 , wherein said biological fluid is serum. 
   
   
       9 . The method of  claim 1 , wherein said subject is a female. 
   
   
       10 . The method of  claim 1 , wherein said subject is a male. 
   
   
       11 . The method of  claim 1 , wherein said at least one antibody is an IgM type antibody. 
   
   
       12 . The method of  claim 1 , wherein said at least one antibody is an IgA type antibody. 
   
   
       13 . The method of  claim 1 , wherein said at least one antibody is an IgG type antibody. 
   
   
       14 . The method of  claim 2 , wherein said anti-Glc (α) antibody is an IgM type antibody. 
   
   
       15 . The method of  claim 3 , wherein said anti-Glc (α 1-4) Glc (α) antibody is an IgM type antibody. 
   
   
       16 . The method of  claim 1 , wherein said diagnosis is an early diagnosis of multiple sclerosis. 
   
   
       17 . The method of  claim 1 , wherein said control sample is determined using an Expanded Disability Status Scale (EDSS) assessment or a Magnetic Resonance Imaging (MRI) assessment. 
   
   
       18 . The method of  claim 1 , wherein said control sample is determined using an Expanded Disability Status Scale (EDSS) assessment. 
   
   
       19 . The method of  claim 1 , wherein said method comprises detecting at least two of said antibodies. 
   
   
       20 . The method of  claim 1 , wherein said method comprises detecting at least four of said antibodies. 
   
   
       21 . The method of  claim 1 , wherein said method comprises detecting at least six of said antibodies. 
   
   
       22 . A method of diagnosing a multiple sclerosis exacerbation in a subject, the method comprising
 providing a test sample from a subject;   detecting an anti-Glc (α) IgM type antibody or an anti-Glc (α 1-4) Glc (α) IgM type antibody in said test sample; and   comparing the levels of said antibody in said test sample to a control sample, wherein said control sample is derived from one or more individuals whose multiple sclerosis status is known,   thereby diagnosing multiple sclerosis exacerbation in said subject.   
   
   
       23 . The method of  claim 22 , wherein said method comprises
 detecting an anti-Glc (α) IgM type antibody in said test sample; and   comparing the levels of said antibody in said test sample to said control sample.   
   
   
       24 . The method of  claim 22 , wherein said method comprises
 detecting an anti-Glc (α 1-4) Glc (α) a IgM type antibody in said test sample; and   comparing the levels of said antibody in said test sample to said control sample.   
   
   
       25 . The method of  claim 22 , wherein said method comprises
 detecting an anti-α-Glucose IgM type antibody and an anti-Glc (α 1-4) Glc (α) a IgM type antibody in said test sample; and   comparing the levels of said antibodies in said test sample to said control sample.   
   
   
       26 . The method of  claim 22 , wherein said control sample consists essentially of a population of one or more individuals in remission multiple sclerosis status that do not show symptoms of a multiple sclerosis exacerbation, and a multiple sclerosis exacerbation is diagnosed in said subject if more anti-Glc (α) antibody or anti-Glc (α 1-4) Glc (α) antibody is present in said test sample than in said control sample. 
   
   
       27 . The method of  claim 22 , wherein said control sample consists essentially of a population of one or more individuals that their multiple sclerosis status in exacerbation, and show symptoms of a multiple sclerosis exacerbation, and a multiple sclerosis exacerbation is diagnosed in said subject if similar anti-Glc (α) antibody or anti-Glc (α 1-4) Glc (α) antibody levels is present in said test sample and in said control sample. 
   
   
       28 . The method of  claim 22 , wherein said test sample is a biological fluid. 
   
   
       29 . The method of  claim 28 , wherein said biological fluid is whole blood, serum, plasma, spinal cord fluid, urine, or saliva. 
   
   
       30 . The method of  claim 28 , wherein said biological fluid is serum. 
   
   
       31 . The method of  claim 22 , wherein said subject is a female. 
   
   
       32 . The method of  claim 22 , wherein said subject is a male. 
   
   
       33 . The method of  claim 22 , wherein said diagnosis is an early diagnosis of multiple sclerosis exacerbation. 
   
   
       34 . The method of  claim 22 , wherein said subject has been treated by subcutaneous administration of interferon beta. 
   
   
       35 . The method of  claim 22 , wherein said subject has been treated by subcutaneous administration of glitamerer acetate. 
   
   
       36 . A method for assessing multiple sclerosis disease severity in a subject, the method comprising
 providing a test sample from a subject;   determining whether said test sample contains an anti-α Glucose IgM type antibody or an anti-Glc (α 1-4) Glc (α) IgM type antibody; and   comparing the level of said at least one antibody in said test sample to a control sample, wherein said control sample is derived from one or more individuals whose multiple sclerosis disease severity is known.   thereby assessing of multiple sclerosis severity in said subject.   
   
   
       37 . The method of  claim 36 , wherein said method comprises
 detecting an anti-Glc (α) IgM type antibody in said test sample; and   comparing the levels of said antibody in said test sample to said control sample.   
   
   
       38 . The method of  claim 35 , wherein said method comprises
 detecting an anti-Glc (α 1-4) Glc (α) IgM type antibody in said test sample; and   comparing the levels of said antibodies in said test sample to said control sample.   
   
   
       39 . The method of  claim 35 , wherein said method comprises
 detecting an anti-Glc (α 1-4) Glc (α) IgM type antibody and an anti-Glc (α) IgM type antibody in said test sample; and   comparing the level of said antibodies in said test sample to said control sample.   
   
   
       40 . The method of  claim 36 , wherein said control sample consists essentially of a population of one or more individuals whose multiple sclerosis disease severity is defined by Expanded Disability Status Scale (EDSS), changes in an EDSS score, or a Magnetic Resonance Imaging (MRI) assessment. 
   
   
       41 . The method of  claim 36 , wherein said test sample is a biological fluid. 
   
   
       42 . The method of  claim 41 , wherein said biological fluid is whole blood, serum, plasma, spinal cord fluid, urine, saliva. 
   
   
       43 . The method of  claim 41 , wherein said biological fluid is serum. 
   
   
       44 . The method of  claim 36 , wherein said subject is a female. 
   
   
       45 . The method of  claim 36 , wherein said subject is a male. 
   
   
       46 . The method of  claim 36 , further comprising selecting a therapeutic agent for treating multiple sclerosis, the method comprising
 determining whether said test sample contains anti Glucose α antibody; and   selecting a therapeutic agent and dosage regimen based on the relative levels of said antibody in said subject sample and said control sample.   
   
   
       47 . The method of  claim 46 , wherein said method further comprises
 determining whether said test sample contains an anti-Glc (α 1-4) Glc (α) antibody; and   comparing the levels of said an anti-Glc (α 1-4) Glc (α) antibody in said test sample to levels of antibody in a control sample consisting essentially of one or more individuals whose multiple sclerosis status is known.   
   
   
       48 . A kit for diagnosing symptoms associated with multiple sclerosis, the kit comprising:
 a first reagent that specifically detects an anti-Glc (α 1-4) Glc (α) antibody;   a second reagent that specifically detects an anti-Glc (α 1-4) Glc (α) antibody; and   directions for using said kit.   
   
   
       49 . The kit of  claim 48 , further comprising a reagent that specifically detects an IgM type antibody.