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.