CBL Chemical Biology Lab

Multiple Slerosis

(MS)

In collaboration with:
Istituto Clinico Humanitas, Milan, Italy
Clinical Immunology, University of Milan Italy
School of Medicine - Department of Internal Medicine, University of California, USA

The molecular mechanisms leading to initiation and perpetuation of Multiple Sclerosis remain largely enigmatic, although it is established that a combination of genetic predisposition and environmental stimulation is required. A role of aberrant post-translational antigen modification has been proposed for MS. Indeed, specifically N-glucosylated synthetic peptides, i.e., [Asn31(N-β-Glc)]hMOG(30-50)], have been demonstrated to be powerful tools for increasing autoantibodies recognition in MS patients sera.

Environmental pathways to autoimmune diseases: the cases of primary biliary cirrhosis and multiple sclerosis, Selmi, C.; Maria Papini, A.; Pugliese, P.; Claudia Alcaro, M.; Gershwin, M. E. Arch. Med. Sci. 2011, 7, 368–380.

 

 

 

 

 

 

 

Different protein autoantigens are associated with MS. In particular, antibodies to Myelin Oligodendrocyte Glycoprotein (MOG) in serum have a dubious prognostic value in MS. The MOG recombinant protein conformational properties relevant to the antigenic activity are unknown. We are currently working on the role of the protein conformation and glycosylation state for the anti-MOG antibody detection. In a first approach, we employed a solid-phase ELISA based on the refolded extracellular domain of rat MOG expressed in E. coli. However, in MS sera and controls up to now we failed to detect IgM or IgG antibodies.

IgG and IgM antibodies to the refolded MOG(1-125) extracellular domain in humans, Gori, F.; Mulinacci, B.; Massai, L.; Avolio, C.; Caragnano, M.; Peroni, E.; Lori, S.; Chelli, M.; Papini, A. M.; Rovero, P.; Lolli, F. J. Neuroimmunol. 2011, 233, 216–220.

 

 

 

 

 

 

 

 

 

Interestingly, we have identified Alpha actinin 1 as a putative antigen based on its recognition by autoantibodies isolated from MS patients’ serum by affinity chromatography based on the N-glucosylated beta-turn peptide CSF114(Glc). Indeed, in a previous work we have shown that this synthetic peptide probe  specifically identifies serum autoantibodies in a subset of MS patients, representing approximately 30% of the patients’ population. 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.

Alpha actinin is specifically recognized by Multiple Sclerosis autoantibodies isolated using an N-glucosylated peptide epitope. Pandey, S.; Dioni, I.; Lambardi, D.; Real-Fernandez, F.; Peroni, E.; Pacini, G.; Lolli, F.; Seraglia, R.; Papini, A. M.; Rovero, P. Mol. Cell. Proteomics 2013, 12, 277–282.