Huge Genetics Study With Treatment Implications Reveals Pathophysiology of MS

[Gemini]

The largest MS genetics study with 115,803 participants--47,429 cases and 68,374 controls--has identified 232 genetic variants as well as the first variant on the X chromosome to be associated with MS susceptibility.

Previous MS research focused on T-cell involvement however, this study expands that view and links the functional consequences of the genetic variants to multiple immune cells (B cells, T cells, NK cells, microglia, etc.) implicating them as contributing to the earliest events in a trajectory of genetic-environmental interaction that triggers MS.

This heterogeneity may lead to new precision medicine treatment strategies i.e., subgrouping MS patients into those who respond to B cell depletion therapies, others who respond to T cell immunomodulatory therapies, etc.

And some of their findings may apply to other autoimmune diseases according to the researchers. ME/CFS researchers should take notice.

The large sample size is impressive, to say the least, as is their Consortium of 60 researchers affiliated with 95 different Institutions/Departments worldwide! And they pooled their funding! Nice work & results!

Multiple Sclerosis Genomic Map Implicates Peripheral Immune Cells and Microglia in Susceptibility, Science, September 27, 2019

https://www.ncbi.nlm.nih.gov/pubmed/31604244

@Hip @Gingergrrl

 

[Gingergrrl]

This heterogeneity may lead to new precision medicine treatment strategies i.e., subgrouping MS patients into those who respond to B cell depletion therapies, others who respond to T cell immunomodulatory therapies, etc.

Thanks for tagging me @Gemini and I agree that precision medicine is the key (since no two patients are the same even if they have been given the same diagnosis). I believe that many MS patients are already being treated with B-cell depleting therapies including some with Rituximab. But I don't know how MS patients are divided into sub-groups for different treatments and have never had that diagnosis.

 

[Gemini]

I believe that many MS patients are already being treated with B-cell depleting therapies including some with Rituximab. But I don't know how MS patients are divided into sub-groups for different treatments and have never had that diagnosis.

Agree, @Gingergrrl. It's exciting MS researchers have linked genetic variants to specific immune cell dysfunction. Wonder if their techniques (GWAS, etc.) could be used to do the same in ME/CFS?

Brings to mind how perplexed Dr. Fluge is as to why some patients responded to Rituximab. He's following David Andersson's research implicating IgG in FM and Ron Davis' nanoneedle "Something in the blood" finding. They might fit in with the emerging MS model (excerpt from Science commentary, 9/27/19):

"Collectively, the results of the [International MS Genetics Consortium] studies lend support to the hypothesis that for most individuals who will develop MS, the disease is likely driven by events in the periphery, which result in the expansion of autoreactive lymphocytes (T cells and B cells)."

If he hasn't seen them already, these MS discoveries may interest Ron Davis @Janet Dafoe (Rose49).

 

[Gingergrrl]

Brings to mind how perplexed Dr. Fluge is as to why some patients responded to Rituximab.

@Gemini I know your original article was re: MS but I just found a really interesting study re: the use of Rituximab in MG (myasthenia gravis) and thought I would add the link here in case it is helpful to anyone.

https://www.neurologylive.com/clini...A7vLR_jqX2zYAzruiWR4TFZvJf-ok5ii9eZ-UYSn6KSd0

The article says:

In the largest retrospective study of rituximab in the treatment of myasthenia gravis (MG) to date, the anti-CD20 monoclonal antibody was shown to be safe, efficacious, and importantly, fast acting

I don't have MG and am not positive for the MuSK autoantibodies like in the study, but I am positive to a very closely related autoantibody (the N-type Calcium Channel Autoantibody that correlates with LEMS) and I was a HUGE responder to Rituximab and my next infusion is in two weeks. I am now doing maintenance infusions 2x per year.

I have talked with many MG and LEMS patients who are not responders to Rituximab which leads me to believe that ALL of these illnesses have sub-groups. I was diagnosed with "CFS" by 5-6 doctors in the US between 2013 and 2016 until it was discovered that I had a boatload of bizarre autoantibodies.

 

[Gemini]

@GeminiI have talked with many MG and LEMS patients who are not responders to Rituximab which leads me to believe that ALL of these illnesses have sub-groups. I was diagnosed with "CFS" by 5-6 doctors in the US between 2013 and 2016 until it was discovered that I had a boatload of bizarre autoantibodies.

@Gingergrrl thanks for posting the interesting MG article describing what's happening in another disease.

Along those lines hope Dr. Avi Nath, an MS expert, is aware of this Science article and will pick up on any of the MS findings that apply to ME/CFS.

Vickie Whittemore speaking at the2019 IIME Conference reported he had significant early results from patients in his NIH Clinical Trial that may lead to treatments--wonder what treatments that could be?

A lead researcher on the MS study, Dr. Patsopoulos, is a Harvard neurologist where we now have Ron Tompkins (thanks to Ron Davis) and Michael Van Elzakker. Given both diseases involve genetic predisposition, immune dysfunction, environmental exposures (i.e., infection) and CNS involvement, wouldn't it be mutually beneficial if they consulted with each other?

Your comment about having "a boatload of bizarre autoantibodies" brought to mind a similar one made by an ME/CFS researcher many years ago that patients seemed to have antibodies to everything. Good that antibody research was featured at this years IIME Conference.

So glad to hear about your positive Rituximab response.