Twin studies revisited


You asked me what do I think of this paper?….Nice sexy science however, I said my bit on this paper last year when it was first submitted

Indeed, we had a look at this paper in October 2019

Like a submarine it has surfaced and there is abit on B cells but the focus is on T cells and a Th17 signature

They say

Immune signatures of prodromal multiple sclerosis in monozygotic twins.Gerdes LA, Janoschka C, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A, Ertl-Wagner B, Barkhof F, Meuth SG, Kümpfel T, Wiendl H, Hohlfeld R, Klotz L.Proc Natl Acad Sci U S A. 2020 Aug 17:202003339. doi: 10.1073/pnas.2003339117

Multiple sclerosis is an autoimmune disease shaped by genetic and environmental factors. Because of the heterogeneity of the human population, it has been difficult to identify “immune signatures” of the disease. Here we investigated a cohort of identical twin pairs who are discordant for multiple sclerosis. In each twin pair, the immune signatures were remarkably similar, pointing to a strong influence of shared genetic and environmental factors. However, when we focused on a subgroup of seemingly healthy cotwins who showed subtle signs of “subclinical neuro-inflammation,” we identified a distinct signature of memory T cells. Insight into the immunological mechanisms associated with the initiation of the disease is relevant not only to the therapy but also for prevention of the disease.

The appearance of symptoms can be preceded by a long-lasting prodromal phase of clinically silent neuroinflammation. This is detected only very rarely and usually only by chance when unexpected silent brain lesions are observed on MRI performed for an unrelated medical reason, a setting referred to as “radiologically isolated syndrome”

 There threy took advantage of a unique cohort of 43 monozygotic twin pairs who are discordant for MS: That is, one cotwin in each pair carries the diagnosis of MS, whereas the other cotwin is clinically healthy. They reasoned that pairwise comparisons of these identical twins would eliminate genetic heterogeneity for each pair, and in addition reduce environmental heterogeneity as the twins included in this study were raised in the same household

The healthy cotwins of MS-affected twins have a maximum familial risk of developing MS and therefore an increased probability of showing signs of prodromal MS. They were able to detect an early influence of MS on the peripheral immune signature, using high-resolution flow cytometry-based immune phenotyping followed by unbiased machine-based analysis.

 In this system immunology approach, 13 9- to 10-color immunophenotyping panels were used for the characterization of major immune cell subpopulations and their maturation and functional status 

They say they identified a distinct signature of memory T cells.

I will say no more. But ask you this.

Look above and below and ask yourself “Does this pass the Smack you in the eye test?”

Is it important? If you were one of the grey dots (CIS) would you have MS like the green dots or would you be healthy like the bluey dots. If you were a cream dot would you be confident you should not be a grey dot.

So what do you think?

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  • Have not read the whole paper

    But they say that the twins that dont got ms ,dont have an “normal” immune t cell compartment

    So if they are really really really equal why one get ms an the other dont

    Almost if you an your twin brother buy a car (an english of course) made in the same factory at the same time by the same group of people

    An one get broken andd the other dont


    • Yes I have read but you will notice I have not commented on the paper, I have given you the punchline data and asked you what do you think. Is it clear that ther is a Th17 issue?

      If you dont look in the right place you can never get the answer

  • Can we estimate the importance of genetic factor if circa 24% of homozygotic twins has MS at the same time? For example as 5 or 10%?

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