Wednesday, February 03, 2016

Factor h and ALS

Lyme has factor H evasion strategies and in innate immunity its role is to amplify the immune response.  I do not believe that lyme is the only pathogen involved in ALS, but that together a group of them with factor H evasion strategies mess up complement and factor H so it no longer does its job properly.

Lyme divides very slowly compared to other bacteria and it forms these "blebs" in response to antibiotics.  Antibiotics do not kill the blebs and there is evidence that the blebs do not come out in the presence of antibiotics.  Lyme is also extremely easy to kill when it is not in the protective bleb form.  Dr Eva Sapi is the foremost expert researcher into lyme, http://www.newhaven.edu/faculty-spotlights/eva-sapi/.

Factor h is a part of complement and lyme can bind to it and hide from the body's innate immunity.  Factor h is responsible for pulling C3b off host cells and it isn't doing its job in the spines of ALS patients.

There is medical evidence that complement, or innate immunity, is involved in ALS.

  • The complement factor C5a contributes to Pathology in a Rat Model of ALS, http://www.jimmunol.org/content/181/12/8727.short, "With end-stage disease, SOD1G93A rats displayed marked deposition of C3/C3b, and a significant up-regulation of the C5aR in the lumbar spinal cord."
  • Complement upregulation and activation on motor neurons and neuromuscular junction in the OSD1 G93A mouse model of familial ALS, http://www.ncbi.nlm.nih.gov/pubmed/21501881, "We determined complement expression and activation in the SOD1 G93A mouse model of familial ALS (fALS). At 126days, C3 mRNA was upregulated in spinal cord and C3 protein accumulated in astrocytes and motor neurons. C3 activation products C3b/iC3b were localized exclusively on motor neurons. At the neuromuscular junction, deposits of C3b/iC3b and C1q were detected at day 47, before the appearance of clinical symptoms, and remained detectable at symptomatic stage (126days). Our findings implicate complement in the denervation of the muscle endplate by day 47 and destruction of the neuromuscular junction and spinal neuron loss by day 126 in the SOD1 G93A mouse model of fALS."
So, the stuff killing the neurons is from complement.  And, lyme can hide from complement, and therefore innate immunity, and it binds to factor H, which is supposed to be protecting host cells.
This paper, Evidence for Fungal Infection in Cerebrospinal Fluid and Brain Tissue from Patients with ALS, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400386/, means that you can not ignore candida in ALS.  Page 552 on this paper, where they talk about the results of looking at the brains of 3 deceased ALS patients, "the most striking finding was that C. albicans appeared in all three patients."  They tested 5 ALS against 3 controls for the spine and the C. albicans antibodies were on average 12 times higher in ALS compared to the controls.  C.famata 5 times, penicillium double, enolase 1.5 times and β tubulin peptide about 4 times the antibodies over the controls.  C.glabrata, C.parapsilosis were about the same in the ALS patients and the controls.
Unfortunately, Candida can also hide from factor H, Immune evasion of the human pathogenic yeast Candida albicansPra1 is a Factor H, FHL-1 and plasminogen binding surface protein, http://www.ncbi.nlm.nih.gov/pubmed/19850343

You also have to ask the question, it the C3b landing on the spine because the candida is there?  I have not seen a study look for lyme on patient's spine, but could that also be a reason for the C3b to be on patient's spine?

The lyme binds factor H via OspE proteins, Outer surface protein E antibody response and its effect on complement factor H bind to OspE in Lyme borreliosis, http://www.ncbi.nlm.nih.gov/pubmed/18248762.
I don't have a reference for this as it was a question I asked an ALS research, but gene expression for factor H is up in the ALS mouse model after the onset of symptoms, but it is unknown whether it is actually being produced, or what is happening to it.  I don't think the mouse model has lyme, but it could have other pathogens with factor H evasion strategies messing it up.
When I learned the stuff clogging up the spines of ALS patients was coming from complement and the role of factor H, I started trying to find pathogens with factor H evasion strategies as it just seemed to me that since there is something wrong happening in innate immunity with ALS, it would be a good idea to look at these other pathogens and be on guard for them, and it also seemed this could be a reason for differences in ALS.
Pathogens with factor H evasion strategies:
  • SteptococcusAcquisition of factor H by a novel surface protein on group B Streptococcus promotes complement degradation, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775014/
  • Salmonella with E.ColiHuman Complement Factor H Binds to Outer Membrane Protein Rck of Salmonella, http://www.ncbi.nlm.nih.gov/pubmed/20622116 (I know of a PALS whose ALS onset was after a food poisoning and he passed away 9 months later.)
  • AspergillusImmune evasion by acquisition of complement inhibitors: the mould Aspergillus binds both factor H and C4b binding protein, http://www.ncbi.nlm.nih.gov/pubmed/17915330
  • B. duttonii, B. recurrentisRelapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H, http://www.ncbi.nlm.nih.gov/pubmed/16790790
  • Haemophilus influenzae, Identification of a Haemophilus influenzae factor H-Binding lipoprotein involved in serum resistance., http://www.ncbi.nlm.nih.gov/pubmed/24835392
  • Neisseria meningitidis, The Factor H Binding Protein of Neisseria meningitidis Interacts with Xenosiderophores in Vitro, http://pubs.acs.org/doi/abs/10.1021/bi301161w
  • Streptococcus pyogenes, Acquisition of complement factor H is important for pathogenesis of Streptococcus pyogenes infections: evidence from bacterial in vitro survival and human genetic association, http://www.ncbi.nlm.nih.gov/pubmed/22140259
This is what I've found.  From what I've seen in the ALS community, Lyme, mold and candida keep coming up.

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