Therapeutic and diagnostic uses of antibody specificity profiles

Abstract

This invention provides a method for determining the antibody specificity profile in an individual. This specificity profile reveals the individual's immune response to multiple antigens and/or epitopes of autoantigens, allergens, graft antigens, etc. The antibody specificity profile is determined through the binding of patient samples comprising antibodies to the arrays. The array can comprises antigens and epitopes. The invention also provides the means and methods for determining antigen or epitope specificity profiles that can be used in the development of either generic and individualized diagnosis and treatment for immune related diseases, including autoimmune disease, allergy and graft rejection.

1 - 37 . (canceled) 
     
     
         38 . A method for determining an antibody specificity profile for a patient with insulin-dependent diabetes mellitus (IDDM) comprising:
 (a) providing an autoantigen array comprising at least two autoantigen elements associated with IDDM wherein each autoantigen element further comprises at least one immunologic epitope(s);   (b) physically contacting the autoantigen array from step (a) with a patient sample comprising antibodies from a patient having IDDM;   (c) identifying the autoantigens associated with IDDM within the array that bind to antibodies within the patient sample from step (b);   (d) comparing the antibodies from the patient sample bound to the autoantigens in step (c) with (1) antibodies from a positive reference or control sample wherein the antibodies from the positive reference or control sample are known to be associated with IDDM; and, (2) antibodies from a negative reference or control sample wherein the antibodies from the negative reference or control sample are not associated with IDDM, thereby determining an antibody specificity profile specific for the patient.   
     
     
         39 . The method of  claim 38  wherein the patient has not developed clinical symptoms. 
     
     
         40 . The method of  claim 38  wherein the patient has clinical symptoms. 
     
     
         41 . The method of  claim 38  wherein the autoantigen array comprises autoantigens selected from the group consisting of protein, polypeptide, peptide, DNA, RNA, lipid, glycosylated molecules, polypeptides with phosphorylation modifications, polypeptides with citrulline modifications, polysaccharides or other molecules. 
     
     
         42 . The method of  claim 38  wherein the autoantigen array is a microarray. 
     
     
         43 . The method of  claim 38  wherein the autoantigen array has addressable elements. 
     
     
         44 . The method of  claim 38  wherein the patient sample is a blood sample. 
     
     
         45 . The method of  claim 44  further comprising the steps of:
 (e) selecting an antigen-specific treatment regimen based on the antibody specificity profile; and, 
 (f) administering the antigen-specific treatment regimen, wherein the antigen-specific regimen comprises administering one or more autoantigens identified in step (c). 
 
     
     
         46 . The method of  claim 44  wherein the antigen-specific treatment regimen comprises administering a protein, a peptide, or DNA encoding the protein or peptide. 
     
     
         47 . The method of  claim 38  wherein the autoantigens are selected from the group consisting of IA-2; IA-2beta; GAD; insulin; proinsulin; HSP; glima 38; ICA69; and p52. 
     
     
         48 . The method of  claim 45  wherein the autoantigens are selected from the group consisting of IA-2; IA-2beta; GAD; insulin; proinsulin; HSP; glima 38; ICA69; and p52. 
     
     
         49 . An antibody specificity profile of a patient afflicted with insulin-dependent diabetes mellitus (IDDM), the antibody specificity profile comprising a spectrum of antibodies in a blood sample from the patient bound to an autoantigen array of multiple autoantigens associated with IDDM wherein the IDDM autoantigens comprise IA-2; IA-2beta; GAD; insulin; proinsulin; HSP; glima 38; ICA69; and p52. 
     
     
         50 . The antibody specificity profile of  claim 49  wherein the patient afflicted with IDDM has clinical symptoms. 
     
     
         51 . The antibody specificity profile of  claim 49  wherein the patient afflicted with IDDM does not have clinical symptoms. 
     
     
         52 . An antibody specificity profile of a patient afflicted with multiple sclerosis (MS), the antibody specificity profile comprising a spectrum of antibodies in a blood sample from the patient bound to an autoantigen array of multiple autoantigens associated with MS wherein the MS autoantigens comprise proteolipid protein (PLP); myelin basic protein (MBP); myelin oligodendrocyte protein (MOG); cyclic nucleotide phosphodiesterase (CNPase); myelin associated glycoprotein (MAG), myelin-associated oligodendrocytic basic protein (MBOP); alpha-B-crystallin; viral and bacterial mimicry peptides; OSP (oligodendrocyte specific-protein); or citrulline-modified MBP. 
     
     
         53 . The antibody specificity profile of  claim 52  wherein the patient afflicted with MS has clinical symptoms. 
     
     
         54 . The antibody specificity profile of  claim 52  wherein the patient afflicted with MS does not have clinical symptoms. 
     
     
         55 . An antibody specificity profile of a patient afflicted with rheumatoid arthritis (RA), the antibody specificity profile comprising a spectrum of antibodies in a blood sample from the patient bound to an autoantigen array of multiple autoantigens associated with RA wherein the RA autoantigens comprise type II collagen; hnRNP; A2/RA33; Sa; filaggrin; keratin; citrulline; cartilage proteins; gp39; collagens type i, ill, iV, V, iX, Xi; HSP-65/60; IgM (rheumatoid factor); RNA polymerase; cardiolipin; aldolase A; citrulline-modified fiaggrin and fibrin. 
     
     
         56 . The antibody specificity profile of  claim 55  wherein the patient afflicted with RA has clinical symptoms. 
     
     
         57 . The antibody specificity profile of  claim 55  wherein the patient afflicted with RA does not have clinical symptoms.