However, has the latest autoantigen in MS been found?
Multiple sclerosis is an autoimmune disease that is caused by the interplay of genetic-, particularly the HLA-DR15 haplotype, and environmental risk factors. How these etiologic factors contribute to generating an autoreactive CD4+ T cell repertoire is not clear. Here, we demonstrate that self-reactivity, defined as “autoproliferation” of peripheral Th1 cells, is elevated in patients carrying the HLA-DR15 haplotype. Autoproliferation is mediated by memory B cells in an HLA-DR dependent manner. Depletion of B cells in vitro and therapeutically in vivo by anti-CD20 effectively reduces T cell autoproliferation. T cell receptor deep sequencing showed that in vitro autoproliferating T cells are enriched for brain-homing T cells.
They looked at cells found in CNS lesions and this consisted of T cells where it seems that the CD8 cells present are abundant in the periphery also suggesting that they were trafficking in perhaps by a bystander mechanisms. However, there were CD4 clones that may have expanded in the CNS. This study elegantly examined the recognition target of the cells and they recognised nucelotide exchange factors (RASGRPs), notabtly RAS guanyl-releasing protein 2. Other people recognised this target too. Is this the cause of autoimmunity in MS?
A nice piece of work that I have yet to adequately digest but I have my doubts.
Based on Message the target is expressed by nerves but it is is also found in other tissues, including lymphocytes. Is this why there is autoproliferation?
Anyway a trial is now planned to block the immune response to this antigen.