In the new era of preprint papers you can put your stuff online, even before it is reviewed.
Todays offering looks at twins, one with MS and one without an MS diagnosis. However when they look at the twin without a diagnosis, they find MRI features that they think could be early MS. These people are in what we call the prodromal phase. In this study they look at the immune component and conclude that T cells hold the key to determining whether MS features occur or not.
The looked at 43 pairs of twins, 22 untreated, 14 on beta interferon, 4 on natalizumab and 3 on glatiramer acetate. Evident of inflammation occured in 10/43 twins. They looked for MS associated signatures in these samples and found them in T cells, notably effector and activated CD4 and CD8 T cells, and not total B cells . This supports the view that MS is orchestrated by antigen-driven T cells.
This was replicated in another population of early MS but there was no impact of MS on peripheral B cell traits, which the y think contradicts the role of B cells, although it is possible that cells not detectably modified by MS can still participate in MS.
Sadly B memory cells never got a mention. Does ths mean that they were not really analysed or that they are unimportant? I guess we will never know unless the reviewer reads this post and asks the question:-( However, time and time again we see studies that only look at T cells, when they could look, report and shut me up:-)
So here we are T cells are king, in an apparently unbiased look. This is all nice science, but I suppose you may ask is, “What is new here?” The authors thought T cells were king before they did this work and they think the same after this study. It does not really move us further forward about knowing what those T cells do. No doubt we will soon see the study where they sequence the T cell receptors of every cell and make the receptors and hunt for specificity, but until then the question I have to ask is why have the T cell specific therapies not done a better job?
Response to therapy is surely the most important experiment in humans and is worth more than T cell rhetoric. That this study cannot explain the response to B cell therapy tends to suggest they are missing something.
So let’s all shout It’s behind you:-)
Gerdes, Lisa Ann and Janoschka, Claudia and Eveslage, Maria and Mannig, Bianca and Wirth, Timo and Schulte-Mecklenbeck, Andreas and Lauks, Sarah and Glau, Laura and Groß, Catharina C. and Tolosa, Eva and Flierl-Hecht, Andrea and Ertl-Wagner, Birgit and Barkhof, Frederik and Meuth, Sven G. and Kümpfel, Tania and Wiendl, Heinz and Hohlfeld, Reinhard and Klotz, Luisa, Immune Signatures of Prodromal Multiple Sclerosis in Monozygotic Twins (September 3, 2019). IMMUNITY-D-19-00879. Available atSRN: https://ssrn.com/abstract=3447318 or http://dx.doi.org/10.2139/ssrn.3447318
ABSTRACT The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like Multiple Sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, we investigated a unique cohort of monozygotic twin pairs who were clinically discordant for MS. Notably, a subgroup of the clinically healthy twins exhibited signs of subclinical, prodromal MS. Comprehensive immune phenotyping revealed that in the overall cohort, the immune signatures of MS-affected and unaffected co-twins were remarkably similar. Twinship alone contributed 68% of the immune variation, whereas age, sex and MS together only Immune signatures of MS in twins 2 contributed 8%. However, distinct traits in CD4+ and CD8+ effector T cell populations emerged when we focused on the subgroup with prodromal MS. These early-disease immune traits were confirmed in a second independent cohort of untreated early relapsingremitting MS patients. Early involvement of effector T cell subsets points to a key role of T cells in MS disease initiation.