Friday, November 27, 2009

The Modus Operandi: Part II

In my previous post, I gave my theory explaining the female predominance of ME/CFS and fibromyalgia, in this post I will explain my theory behind the neurological symptoms of ME/CFS, FM, and Autism.  My theory centers around the SYG1 membrane protein, which has been identified as a synaptic guidepost, directing neurons to connect to each other.  The SYG1 protein is in the immunoglobulin superfamily, with an extracellular domain, a single transmembrane segment, and an intracellular loop.  SYG1 binds to its receptor SYG2, which is also a member of the immunoglobulin superfamily.  Ironically, SYG1 is most heavily expressed during fetal development and early childhood, and its expression greatly diminishes thereafter.  In adulthood, it continues to be expressed in the limic region (which includes the hypothalamus), at neuromuscular junctions in skeletal muscle, and in arterial walls.  When it is activated, it initiates selective synapse elination through the SCF-Ubiquitin ligase complex - when it works properly, SYG1 binds to SKR, inhibiting formation of the SCF complex (Skp1-cullin-F-Box complex), protecting nearby synapses.

It is my opinion that SYG1 dysregulation is directly correlated to symptoms noted in all three conditions: ME/CFS, FMS, and Autism.  If you disrupt proper synapse formation in early childhood development, you almost certainly will end up with a developmental disability.  It leads me to theorize as some have that XMRV is passed from mother to child through saliva, body fluids, breast milk, and quite possibly placental transmission.  Likely the process of autism begins well before the first symptoms appear, and with XMRV screening could be reversed by early use of antiretrovirals, either by treating an infected mother, or the child.  There has been some mention by Dr. Mikovits that vaccines could create the immune insult setting off autism, however I believe the risk is far, far smaller than the immune insult from getting sick - as you are only exposed to an antigen at a point in time, as opposed to receiving a continuous onslaught of viral antigen while the immune system clears the virus.

Another interesting point is that SYG1 is primarily expressed in slow sodium fibers in the peripheral nervous system at neuromuscular junctions- nerve fibers responsible for transmission of pain signals - leading to an amplified pain response.  Substance P opens slow sodium channels, and closes potassium channels - and if you've got uncontrolled synapse formation, it may very well explain some of the observations made in FMS.


  1. Hi Dr Luckett. Thanks for your very informative blog. If you'd like to join us over on the discussion boards at Phoenix Rising CFS (, I know your expertise would be much appreciated.

  2. very interesting, thanks for sharing. one thing though, it must be pointed out that vaccines are rarely, if ever, administered one at a time.

    standard childhood vaccination practice is 3, 4 or (many) more vaccines at once. therefore it is pointless in this context to compare effects of vaccination (as they happen in real life) to getting infected by a SINGLE wild virus. add to that still largely unknown effects of various vaccine adjuvants from those combined vaccines administered in a single setting, and we are really talking uncharted territory here.

  3. Dr. Luckett, Thank you so much for this. It's all very frightening. My husband and I both have had CFS. We have a just three-year-old boy who seems very neurotypical and healthy at this point. But we are talking about having another child within the next year--before, I'm guessing, we'll know too much more about all of this. Is there anything we can do to protect this child?

  4. Thanks for the time you take to help us, help our kids!!! (smile)

  5. Thank you so much for taking the time to explore this issue.

    Do you have any idea if XMRV inhibits DPPIV (like HIV do)?

    If so, that might explain why so many autistics and CFS/ME sufferers do have a positive response to gluten and casein free diets. DPPIV is partly responible for the breakdown of prolinrich peptides from proteins, and with DPPIV inhibited the peptidstrains with opioid action from casein and gluten are not broken down, but exposed to the cells in the intestines (and might interfer with the opioid system in the body, as 5HT reseptors).

    Any thoughts about this?

  6. About DDPIV affected by XMRV - Dr. Klimas reported a significant expression of CD26+ DPP (IV) activated cells in CFS subjects.

    Klimas NG, Salvato FR, Morgan R, Fletcher MA. (1990) Immunological Abnormalities In Chronic Fatigue Syndrome. J. Clinical Microbiology. (6) 1403-10.

  7. Thank you for the reference FR.
    My thoughts: The Klimas study looked at CD2 cells (NK and T- cells ?) expressing CD26/DPPIV, but plasma levels and expression of DPPIV in mucosal cells was not studied. CD26 is thought to be involved in B cells activation, and makes sence in a body with viral infections.

    In another study (Detel D, Serum and intestinal dipeptidyl peptidase activity in children with celiac disease) they compared celiac with malabsorption syndrome and they found lesions in both groups (two different lesion-types, and celiac depending on HLA-DQ types), and low levels of DPPIV correlating to grades of lesions. (This might wery well apply to other patients as well.)

  8. Dr Luckett
    Thanks for all the great info. I am a male who has had CFS for 22 years.I have 2 children both boys.Both ofmy boys are on the autism spectrum. They are high functioning. One has PDD-NOSthe other Aspergers. I am very interested in a possible XMRV-Autism connection. Keepupthe good work on your blog!

  9. Excellent blog. I have had chronic reactivation of HHV infections my entire life, have colitis, arthritis and recently was dx'd with an ASD while trying to get a CFS dx. I'm not a hypochondriac as I've been accused of being, just a sick person searching for answers. Thank you.