Thread by @microbeminded2

Hey! I have some thoughts on the paper below that attempts to position #ME/CFS as an “autoimmune disease” by associating 2 SNPs with very small odds ratios to differences b/t infectious & noninfectious disease onset (OR=0.54 & OR=0.64): frontiersin.org/articles/10.33…

2/ The team didn’t study the #ME/CFS immune response itself, but instead measured several common #SNPs associated w/ certain “autoimmune” conditions in their ME/CFS subjects. For example SNPs in the gene PTPN22 (connected to #Crohn’s, type 1 #diabetes etc)

3/ PTPN22 is a gene that, in simple terms, plays a role in regulating B and T cell activity. It’s actually just a gene that impacts the immune response (there doesn’t HAVE to be anything “autoimmune”-inducing about PTPN22 activity)

4/ In fact, conditions already tied to PTPN22 activity like Crohn’s/type 1 diabetes are being re-evaluated as #microbiome/#pathogen-driven disorders, in which any “autoimmune” activity is tied to cross-reactivity b/t host and pathogen peptides

5/ For examples of that trend read this recent paper on microbiome/pathogen activity in Crohn’s disease: nature.com/articles/s4158… and/or this paper on microbiome activity in type 1 diabetes: ncbi.nlm.nih.gov/pmc/articles/P…

6/ In fact, PTN22 SNPs are widely studied as determinants of how the immune system can respond to persistent #pathogens. Indeed, the PTPN22 SNP tied to #ME/CFS infectious onset in the original study can increase susceptibility to #mycobacteria infection: ncbi.nlm.nih.gov/pmc/articles/P…

7/ So I encourage the authors of the #ME/CFS paper to go a step further and ask “do the PTPN22 and related SNPs we identified confer any survival benefit to the #pathogens known to have infected patients in the study?”

8/ For example, some patients in the study developed ME/CFS after #EBV infection. And EBV is a persistent pathogen that infects B cells in a latent state. Certainly then, SNPs that alter PTPN22 activity cld impact correct management of EBV by the immune system

9/ B/c the #ME/CFS study concludes by stating that their findings "prompt us to intensify research into autoimmune mechanisms and perform clinical studies with drugs targeting autoreactive B cells."

10/ And I couldn't disagree more. Due to the issues I discussed above (and more I could mention) there is no rationale whatsoever to trial immunosuppressive drugs (like rituximab) in patients with #ME/CFS based off the findings