Autism risk genes tied to infectious agents !

[natasa778]

A genetic autism study that actually makes sense - a long time coming but better late than never. Excuse my modesty ;-) but I have been 'predicting' for a long time that there will be 'autism gene risk' linked to various chemokine receptors. And this is exactly what they found …


http://www.plosone.org/article/info:doi/10.1371/journal.pone.0048835

Long and detailed paper, here are highlights:

".. . it is striking that .. there is a loss of genomic copies in the interferon alphas … and gain of copies in the “C-C” motif chemokine ligands...

Several of these chemokines have been found to be overexpressed in inflammatory diseases such as ulcerative colitis [30], atopic dermatitis [31], rheumatoid arthritis [32], and in neurocognitive disorders [33]. This suggests an etiological basis for the disordered innate immunity response found in autism [34], particularly as mediated by monocytes and the histologically related microglia. The loss of interferon alpha copies, usually implicated in the response to viral infection and another component of innate immunity, could also account for a dysregulated, secondary or compensatory response of interferons and chemokines. Several of these messengers “…are produced by neurons and glia in the adult brain, and that they can acutely influence synaptic transmission.”

… The above could be suggestive of a link between in utero infections and brain development in the child. Thus, the genetic background by itself would not be enough via this view to cause a deranged developmental process which would rather only occur in the presence of relevant infections. Interferons are important in the control of viral infections via the induced expression of interferon-stimulated genes [40]. The loss of copy number in the interferon genes suggests a possible reduced expression of such genes when stimulated. Thus, a viral infection would last longer under such a genetic background. Viral infections also lead to the expression of various chemokines in the CNS [41]. Further, chemokines are also involved in brain development [27], [41]. There would therefore be a longer generation of chemokines and other cytokines that could interfere with normal brain development. Further, gain in copy number in chemokines may lead to higher levels of these chemokines and would thus exacerbate the derangement in brain development.

Now the really interesting thing is that retroviruses LOVE to insert themselves in host chemokine receptor genes (and I suspect interferon ones?-anyone knows?). Given the recent finding of reactivated HERVs in autism, it would be very interesting in someone now looked into HERVs expression in parents, including germline - wondering if something like this could account for CC and interferon copy number variations.

It would also tie in with high incidence of auto/immune diseases in autism first degree relatives...

 

[anciendaze]

I have also felt infectious agents were involved. While it would make life simple if we could tie one pathogen like a retrovirus directly to the immune response I'm more and more convinced most of the pathology stems from a misdirected response to secondary infections or common bacteria and viruses normally tolerated. This turned up in an experimental model in mice. (See the review below.)
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-065X.1995.tb00072.x/abstract

The retrovirus, in this view, might trigger the process, but the clinical symptoms would not develop in the absence of other immune challenges. The virus is deliberately misdirecting response to benefit itself. By infecting cells of the immune system it can not merely hide itself from immune defenses, but gain safe replication via clonal expansion of infected cells.

 

[natasa778]

I have also felt infectious agents were involved. While it would make life simple if we could tie one pathogen like a retrovirus directly to the immune response I'm more and more convinced most of the pathology stems from a misdirected response to secondary infections or common bacteria and viruses normally tolerated.

That is exactly my suspicion - retroviral infection or HERV activation (whether in germline or perinatally) lays ground for this 'misdirected response to secondary infections' ?

 

[Enid]

Thanks natasha - no doubts something viral causing immume collapse (genetics may play a part in predisposition to) Brother ME, cousin FM.

 

[natasa778]

Sciencedaily article on the findings http://www.sciencedaily.com/releases/2012/12/121206203417.htm

... Interferons help control viral infections, so reduced production of interferons could delay control of a viral infection in a pregnant woman and her fetus. Viral infections also induce the production of chemokines, which have an additional role in fetal brain development. A combination of reduced interferon levels, which would prolong the course of a viral infection, and elevated chemokine levels could potentially alter brain development in an infected fetus. The researchers are continuing to investigate how these and other immune pathways may be involved in the development of autism.

 

[GcMAF Australia]

bacterial infections and gut inflammation may also play extensive roles.
It is interesting that GcMAF is being used to modify the immune system and help with autism