RE: MS and MODI113 Jan 2020 22:19
Dalestar
The article was saying that one of Lindy's main drivers (probably the main one) was understanding what was causing the immune system to attack healthy cells in RA patients. She learnt that citrullinated proteins were being attacked by the immune system.
Once she had an understanding of this she argued that citrullinated proteins may also exist in cancer tumours and they might present good targets.
What probably surprised her was that her vaccine activated a type of TCell that previously was not considered an important part of the immune system - the CD4+ cytotoxic TCells.
She also found that the CD4+ Tcells caused more stress in the tumour, resulting in more citrullination of proteins (via PAD expression and autophagy)
The article says
"CD4+ T cells specific to citrullinated peptides have been shown in autoimmune patients with RA, T1D and MS as well as during influenza viral infection [62]. "
The whole process with RA starts with the expression of PAD enzymes. Lindy discovered that tumours also over express PAD enzymes. In both diseases this leads to citrullinated proteins.
So one approach in RA is to block the PAD enzymes, thus preventing the citrullination of the proteins.
Lindy is doing the opposite. She is targeting the citrullinated proteins (or rather citrullinated epitopes within the proteins)
With MS, citrullination also seems to be important as this article describes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1794624/
So Lindy's work is not directly applicable to auto immune diseases.
However, what it probably does is give a much better understanding of processes that result in citrullination.
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