Distortion of the Self-Reactive IgG Antibody Repertoire in Multiple Sclerosis as a New Diagnostic Tool

Abstract

To date, none of the myelin-associated Ag targets definitively discriminates between the immune response observed in multiple sclerosis (MS) patients and healthy subjects. However, it has been shown recently that analysis of global immune Ab profiles such as natural autoantibody reactivities can help to distinguish between normal individuals and patients suffering from various immune diseases. The aim of our study was to compare the global IgG immune response against brain self-Ags in sera from 82 MS patients and 27 healthy subjects. The analysis of the immune profiles was performed by Western blotting, and data were subjected to linear discriminant analysis. Particular patterns of IgG reactivity were found in healthy subjects, Sjögren patients, and MS patients. Moreover, this approach separated the three clinical forms of MS with a high concordance rate with the clinical data (κ value, 77.8%). Our study suggests, for the first time, that serum IgG Ab repertoires are able to distinguish MS patients. In addition, our data suggest that patterns of IgG reactivity could model the pathological processes underlying the various forms of MS. Further characterization of such discriminant Ags could provide useful information regarding their potent role in pathogenesis or regulatory processes in MS.

Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis

“…Thus, the serum autoantibodies to linear epitopes might ref lect the specificity of an ongoing T cell response. Note, however, that low-affinity autoantibodies are present in healthy individuals, and changes in the reactivity of these autoantibodies have been described in several autoimmune disorders including MS (40,41). It is now recognized that MS is a complex heterogeneous immunologic disease (1).…”

Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach

“…Eleven of these 16 antigens had already been identified in our previous study (21), in which only MS patients, SS patients with CNS involvement, and healthy subjects were compared. Five new antigenic targets were found in the present study, which included SLE patients and SS patients without CNS involvement.…”

“…Brain sample homogenization and 1-dimensional protein separation were performed essentially as described previously (21). Briefly, 100 mg of brain tissue was homogenized in a detergent solution (4% Triton X-100 and 1ϫ antiprotease cocktail [both from Sigma]) before protein precipitation using 3 volumes of ice-cold acetone.…”

Protéomique et auto-anticorps

“…Il est ainsi possible de traiter en même temps un grand nombre de substrats protéi-ques et de les immunocribler par un grand nombre de solutions d'auto-anticorps. Les profils auto-antigéniques produits sont analysés par des outils statistiques à variables multiples qui, de manière tout à fait similaire à l'approche SELDI, rendent cette technologie particulièrement adaptée à la recherche clinique [24][25][26][27].…”