Is MS an autoimmune disease…It is difficult to confirm this view and disease needs to e controlled by antigen-specific means to e more compelling. This study hunted and found 4 antigens that could induce T cell responses and some showed the capacity to induce histological disease. The study seems to re-affirm that the typical myelin antigens favoured by many immunologists give no better responses than found with the new candidates. The conclusion is that T cells are more important than B cells in MS
Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis.Bronge et al. .Sci Adv. 2022;8:eabn1823.
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role. Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins. We identified four previously unreported autoantigens in MS: fatty acid-binding protein 7, prokineticin-2, reticulon-3, and synaptosomal-associated protein 91, which were verified to induce interferon-γ responses in MS in two cohorts. Autoreactive profiles were heterogeneous, and reactivity to several autoantigens was MS-selective. Autoreactive T cells were predominantly CD4+ and human leukocyte antigen-DR restricted. Mouse immunization induced antigen-specific responses and CNS leukocyte infiltration. This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS.
Here “Antigens were chosen among proteins selectively expressed in the CNS but not previously described as established autoantigen….63 different proteins were….used to stimulate peripheral blood mononuclear cells (PBMCs) from natalizumab-treated persons with MS”.
When I see these types of papers I look to see where the target is expressed using public databates that anyone can look at.
http://www.allenbrain altas X10 expression of message in human brain (dark ble no expression), yellow expression. SNAP91 and RTN3 are nerve markers and low levels on gli,a PROK2 is essentially nothing in CNS and in BioGPS.org, PROK2 is on neutrophils and some lymphocytes and FABP7 is on a few nerves
And as for protein we can look at the protein atlas.org
So you need to ask yourself would you expect a prominant white matter lesional profile with loss of oligodendrocytes as seen in MS given the expression of protein above? However you also have to consider that in MS ssome proteins are upregulated and could then become targets
In the paper they found that “The responses were heterogeneous, and individual patients displayed unique autoreactivity profiles, with different magnitudes of response and combinations of autoantigens”. So there was a variety of responses to different proteins. But if people had responses to these proteins and also some myelin proteins it was more likely they had MS.
They looked for antibodies to the proteins and about 30% of people with MS and controls both responded to RTN3 but others were rare. So they can find some T cells that will respond to these proteins and next up they induce autoimmunity in mice, which develop histological disease. We have shown in the past that you can get disease in mie if you immunize then with CNS expresssed proteins.
Once you find autoantigens the key is to show they are important in humans can this be done…Its being tried.