Wednesday, January 28, 2015

What would studying twins could tell us about immune system? Nothing much.

Few weeks ago journal Cell published a study that was widely publicized by online media. The research article came from Mark Davis lab at the Stanford University School of Medicine.

The authors found between 58%-77% of analyzed immune markers are mostly or solely determined by non-heritable, environmental factors. These data suggest that one cannot predict the magnitude and class of the immune response (TH1,TH2,...etc) based on inherited gene analyses. In other words, these results would make studying immune-related therapies, like vaccine efficacy or anti-tumor immunology, more complicated and unpredictable.
However, these results were expected, anyway. The point is that immune system and especially the antigen-specific repertoires of adaptive immune system (TCR and BCR) are generated stochastic fashion, even in MZ twins. Unique adaptive immune system affects innate immune system as well. Basically, no humans would have the same immune system, everThese implies that neither genes nor environment could truly influence or determine the true direction of immune response. It will be random and individualized response. Only immune system and neuronal system have this additional, random, person-specific level of variation.

Interestingly, the authors themselves acknowledge this point in the discussion, however they dismissed it, as not sufficiently significant.

David Usharauli



  1. David, you should know that nothing is truly random, we can't even generate an algorithm that produces random output. Everything is dependent on, and predictable based on prior conditions; even this blog post!

  2. Thanks for your comment.

    Would you mind clarify which aspect of randomness are you referring to? TCR / BCR rearrangement or immune response?

    I would assume the latter one. I agree mostly that "Everything is dependent on, and predictable based on prior conditions;". The point I was making is that right now we can't truly know what all those "prior conditions were or are". Thus predictability is low, and may appear as "random".

    For me, the most important aspect of this research, that was completely ignored in discussions elsewhere, was that these results would makes our effort to design more optimal vaccines more complicated.

  3. I agree with your comment here, but they contradict your previous conclusion that "neither genes nor environment could truly influence or determine the true direction of immune response". One can conclude that the biology (including genetics) and environment (past and present) are the sole determinants of the outcome. This also of course applies to TCR and BCR.

  4. Thank you for participating in discussion.

    In my opinion, your commentary is only valid:

    1. If we would know every T cells and every B cells receptors in MZ twins by sequencing. Since we don't and probably would be very hard to get every T cells or B cells' exact specificity, then "randomness" would still exist.

    2. If we could predict TCR or BCR specificity by simple knowledge of VJD germline sequences. However, we can't know that by simple "gene" sequencing analysis.

    So, in summary, since right now we can't truly know neither every TCR/BCR' genes or their specificity, nor what all those "prior conditions were or are", my conclusion that for us "immune response" in people, including twins, would appear as "random" is still stands.

  5. My point is simply that appearances are deceiving. There is no randomness, even if there appears to be. Thus, my point also still stands. The biology and the environment alone determine the outcome. That we don't know all the necessary information to make predictions does not invoke a requirement for a magical randomness.