Alpha Actinin is Specifically Recognized by Multiple Sclerosis Autoantibodies Isolated Using an N-Glucosylated Peptide Epitope
Abstract
Sophisticated approaches have recently led to the identification of novel autoantigens associated with Multiple Sclerosis (MuS), 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 MuS 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 MuS patients, representing ∼30% of the patient population. The autoantibodies, purified from MuS 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 MS/MS 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 MuS autoantibodies, or monoclonal antibodies. Further discrimination among the rat brain proteins was provided by the following procedure: whereas monoclonal antibodies recognized all rat brain proteins, isolated MuS specific antibodies recognize only alpha actinin 1 as a putative antigen. In fact, alpha actinin 1 displayed a robust immunoreactive response against all MuS 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 MuS autoantigen, perhaps a prototypic biomarker for the inflammatory/degenerative process typical of the disease.
Related
- An N-Terminally Acetylated Degron Specifically Recognized by the CTLHMKLN1-FAM72A E3 Ubiquitin Ligase for Regulatory Protein Degradation
- Functional microbiome shifts are associated with neuroinflammatory outcomes under dietary interventions in multiple sclerosis
- Effectiveness of Native and Enhanced Extracellular Vesicle Preparations Assessed in Animal Models of Multiple Sclerosis: A Meta-Analysis
- Limited Gut Microbiome Differences Between Relapsing–Remitting and Secondary Progressive Multiple Sclerosis: A Shotgun Metagenomic Study
- Lesion-specific circular RNA and mRNA signatures in secondary progressive multiple sclerosis.
BibTeX
@article{pandey2026alpha,
title = {{Alpha Actinin is Specifically Recognized by Multiple Sclerosis Autoantibodies Isolated Using an N-Glucosylated Peptide Epitope}},
author = {Shashank Pandey and Ilaria Dioni and Duccio Lambardi and Feliciana Real-Fernandez and Elisa Peroni and Giulia Pacini and Francesco Lolli and Roberta Seraglia and Anna Maria Papini and Paolo Rovero},
journal = {Molecular and Cellular Proteomics},
year = {2026},
month = oct,
doi = {10.1074/mcp.m112.017087},
url = {https://hal.science/hal-05779844v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Alpha Actinin is Specifically Recognized by Multiple Sclerosis Autoantibodies Isolated Using an N-Glucosylated Peptide Epitope
AU - Shashank Pandey
AU - Ilaria Dioni
AU - Duccio Lambardi
AU - Feliciana Real-Fernandez
AU - Elisa Peroni
AU - Giulia Pacini
AU - Francesco Lolli
AU - Roberta Seraglia
AU - Anna Maria Papini
AU - Paolo Rovero
PY - 2026
DA - 2026/10/05
JO - Molecular and Cellular Proteomics
DO - 10.1074/mcp.m112.017087
UR - https://hal.science/hal-05779844v1
AB - Sophisticated approaches have recently led to the identification of novel autoantigens associated with Multiple Sclerosis (MuS), 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 MuS 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 MuS patients, representing ∼30% of the patient population. The autoantibodies, purified from MuS 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 MS/MS 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 MuS autoantibodies, or monoclonal antibodies. Further discrimination among the rat brain proteins was provided by the following procedure: whereas monoclonal antibodies recognized all rat brain proteins, isolated MuS specific antibodies recognize only alpha actinin 1 as a putative antigen. In fact, alpha actinin 1 displayed a robust immunoreactive response against all MuS 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 MuS autoantigen, perhaps a prototypic biomarker for the inflammatory/degenerative process typical of the disease.
SN - 1535-9476
SN - 1535-9484
ER -