Research: Actinin alpha 1 a new target or biomarker

EpubPandey et al. Alpha actinin is specifically recognized by multiple sclerosis autoantibodies isolated using an N-glucosylated peptide epitope. Mol Cell Proteomics. 2012 Nov 8.

Sophisticated approaches have recently led to the identification of novel autoantigens associated with Multiple Sclerosis (MS), e.g. neurofascin, contactin, CNPase and other T cell receptor membrane anchored proteins. These putative antigens, although differing from the conventional myelin derivatives, are conceptually based on an animal model of experimental autoimmune encephalomyelitis. In this report we describe the identification of putative antigens based on their recognition by autoantibodies isolated from MS patient serum. In a previous work from this laboratory we have shown that a peptide probe, named CSF114(Glc), specifically identifies serum autoantibodies in a subset of MS patients, representing approximately 30% of the patient population. The autoantibodies, purified from MS patients' sera (six), through CSF114(Glc) affinity chromatography, detected three immunoreactive protein bands present in the rat brain. Proteomic analysis of the immunoreactive bands, involving MALDI and Mass spectroscopy techniques, revealed the presence of four proteins distinguishable by their mass: alpha fodrin, alpha actinin 1, creatine kinase, and CNPase. The immunoreactive profile of these rat brain proteins was compared with that of commercially available standard proteins by challenging against either CSF114(Glc) purified MS autoantibodies, or monoclonal antibodies. Further discrimination among the rat brain proteins was provided by these procedure: whereas monoclonal antibodies recognized all rat brain proteins, MS specific isolated antibodies recognize only Alpha actinin 1 as a putative antigen. In fact, Alpha actinin 1 displayed a robust immunoreactive response against all MS patients sera examined, whereas the other three bands were not consistently detectable. Thus, alpha actinin 1, a cytoskeleton protein implicated in inflammatory/degenerative autoimmune diseases (lupus nephritis and autoimmune hepatitis) might be regarded as a novel MS autoantigen, perhaps a prototypic biomarker for the inflammatory/degenerative process typical of the disease.

This study reports an antibody response to Actinin alpha 1 in MSers. Is it a cause for autoimmune attack or a consequence of tissue damage releasing the protein?. I suspect the latter but will need to be confirmed by the Biomarker Brigade.

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