FINALLY AN AUTOANTIGEN - And gut microbioma connections.
Posted: Thu Oct 18, 2018 3:06 am
Before I was completely sure about MS not being autoimmune. Well, maybe I was wrong.
Let's see if this report is confirmed.
http://stm.sciencemag.org/content/10/462/eaat4301
GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis
The article is freely available here (https://www.zora.uzh.ch/id/eprint/15883 ... _press.pdf) but there is also a nice review here:
https://davidusharauli.blogspot.com/201 ... l.html?m=1
Abstract
Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood.
By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)–l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide.
These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.
Let's see if this report is confirmed.
http://stm.sciencemag.org/content/10/462/eaat4301
GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis
The article is freely available here (https://www.zora.uzh.ch/id/eprint/15883 ... _press.pdf) but there is also a nice review here:
https://davidusharauli.blogspot.com/201 ... l.html?m=1
Abstract
Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and likely requires environmental triggers. The autoantigens and molecular mimics triggering the autoimmune response in multiple sclerosis remain incompletely understood.
By using a brain-infiltrating CD4+ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, we have identified guanosine diphosphate (GDP)–l-fucose synthase as an autoantigen that is recognized by cerebrospinal fluid–infiltrating CD4+ T cells from HLA-DRB3*–positive patients. Significant associations were found between reactivity to GDP-l-fucose synthase peptides and DRB3*02:02 expression, along with reactivity against an immunodominant myelin basic protein peptide.
These results, coupled with the cross-recognition of homologous peptides from gut microbiota, suggest a possible role of this antigen as an inducer or driver of pathogenic autoimmune responses in multiple sclerosis.