Characterization of Humane Autoantibody Response to Brain Proteins in Multiple Sclerosis Patients
Multiple sclerosis (MS) is a neurodegenerative disease, where chronic inflammation plays a central role in the pathology. MS has been described as an autoimmune disease due to the nature of inflammation, which has shown similarities to other autoimmune diseases such as rheumatoid arthritis. A key shared feature present in MS is the induction of autoantibodies stimulated by altered peptide ligand responses and progression by epitope spreading causing loss of tolerance for native peptides. In numerous studies, the idea concerning involvement of autoantibodies in pathogenesis have been suggested to initiate and drive the inflammatory progression in autoimmune diseases, however the etiology is not fully understood.
Methods: Oligoclonal bands (antibodies) have been identified and correlated with disease progression in MS patients. However, previously studies have not been able to identify the antigens recognized by the autoantibodies. We have observed autoantibody responses in diseased animals in both rat and mice experimental autoimmune encephalomyelitis models of MS. After treatment with Etomoxir, a change in autoantibody response has been seen. In addition, autoantigens recognized by the autoantibodies were identified utilizing mass spectrometry based proteomics. Based on these observations in animal models we now analyzed serum and CSF of patients suffering from relapsing-remitting and secondary progressive MS using Western Blot analysis and immunoprecipitation of brain proteins recognized by these antibodies. Thereby, we mapped the antibody response in human MS patients against human brain proteins using proteomics.
The results showed that the antibodies present in the CSF are of the IgG2 isotype. Antigens recognized by autoantibodies are being analyzed by mass spectrometry, thereby trying to identify the proteins targeted in the inflammatory process of MS.
Identification of the proteins targeted by autoantibodies in MS patients makes it possible to generate an overview of the inflammatory process. The target and spreading of the autoantibody response as well as the identification of the underlying T cell response co-stimulating the antibody response is of invaluable importance. With this knowledge we will be able to generate biomarkers for diagnosis, prognosis, and progression of the disease as well as candidate targets for novel drug treatment.