Tuesday, November 16, 2021

Complement in ALS

Today marks 4th anniversary of losing my beautiful and so special sister Norma.  

Christmas 2013, the last year without neurological symptoms, 
my brother Guy, my sister Norma, myself and my nephew Dakota.

Norma's 50th birthday.  A trained eye can actually see problems in her 
arm muscles.  Unfortunately doctors are poorly trained to see this.

Norma traveled the world with ALS, raising ALS awareness
and later volunteering to be in a feeding tube awareness poster.

To honor my sister this year, this is a post about complement, a subjected I started to study very shortly after we knew Norma was battling ALS.  Studying complement led me down a very different path and belief system about ALS, and it also enabled me to make some correct predictions about ALS.

My currently belief about ALS is that chronic infection is playing a role, and it can come from many sources, but mostly likely the interaction of 2 or more kinds of infection simply turns innate immunity down so the body never clears the infection, but over the longer term, the inflammation that goes with the infection depletes storage levels of amino acids and minerals, and some of these microbes can actually block the krebs cycle, causing mitochondrial dysfunction and hypermetabolism, where the body is getting energy from less efficient sources.  Infection also cause increased demand for aromatic amino acids and some minerals to compensate at level that is out of balance with diet and the body's ability to keep up.  So the body is depleted and struggling, and then a tipping point event happens which could be a broken bone, surgery, another infection, etc.

ALS is slow developing disease, but almost the entire focus of research and treatment for ALS is entirely end stage of the disease.  My sister had gut health issues and problems with viruses and fungal infection 20 years ahead of ALS, and I remember talking with her before ALS was even on the table about the void in the medical system to offer any intervention to treat these issues.  In response, my sister developed extremely good dietary habit and a pretty clean lifestyle.  I am so grateful to her for doing this because even though she is gone, I am sure that I'd have lost her sooner without her significant efforts to look after herself.

PALS always feel better when infections are treated, but the process of rebuilding all of the damaged systems is extremely slow and the challenge is how to rebuild faster than the natural breakdown in a broken system.

So today I honor my dearly loved and missed sister with a closer look at complement.  Because I believe the body is so far out of balance nutritionally, I don't hold much faith in the medical community because of gross lack of recognition of this problem.  

I do want to mention two people, Martin Munzer who make leap2bfit.  Amino acids are out of balance and leap2bfit is an exceptionally well designed and balanced single amino acids formulation.  This video, https://nobelmedia.akamaized.net/flashcontent/announcement_2016_med-interview_01_496.mp4, is about the 2016 Nobel prize in medicine for autophagy it explains that body needs about 200 grams of protein per day, with about 2/3rds being recycled protein already in the body.  So a huge problem with amino acid imbalance is how to get the right amino acids for the cells to use.  There is also research showing that in ALS the body is way behind on breaking down proteins, which is likely linked to the mitochondrial dysfunction, and some amino acids are low.  So because of the amino acid dysregulation, I believe leap2bit can help (leapxx.com).  There is one documented ALS case of a pALS who was on a trache that ended up having surgery to remove his trach about two years after starting leap2bfit.  They do not put in temporary trachs for pALS because this just doesn't happen with ALS.  He was also taking several hundred dollars per month of other nutritional supplements.  Hundreds of pALS have been gifted some leap2bfit so they can at least try it and many feel increased energy, improvements in swallowing, and just feeling better.

Martin has such compassion for pALS and their caregivers, he's currently working on fundraising to build an ALS wellness center in Columbia where pALS and caregivers will be looked after and holistic strategies will be available at super reasonable prices.  There will also be an education component for strategies that help to reduce inflammation.  Depending on how fundraising goes, phase I could be ready in a year.  Everyone who has been through ALS knows how hard the disease is on the whole family unit and the ALS wellness center goal is to provide relief for whole family with good food, nutritional supplements, holistic strategies like massage, sauna, acupuncture, etc. all there and affordable because of the low cost of living.  The plan is once this wellness center is up and running, it is able to sustain itself and is not reliant on funding to cover operational costs, but fundraising is required to build the wellness center.  I will update with the website for information and donations as soon as it is released.

Amy Jaramillo, the Scientific Director and founder of BodyScience in Miami, Florida is the other person I'd like to mention.  Amy's knowledge of cell metabolism is second to none and it is exactly what pALS need.  She works on strategies to get those mitochondria working again and she looks deeply for infection and how to treat it.  She has one documented ALS reversal and I'm sure she will have more.  The way ALS is dealt with by the medical community essentially with stewardship for the disease (neurologists) is insane and in my mind, it is negligence to not even trying to help pALS to live and adopting a "there's nothing you can do attitude."  At no point did my sister have a complete medical work-up and no attempts were made to help her correct problems.  It is 34 years since serious liver dysfunction was first documented in ALS and my sister's neurologist was adamant the liver had nothing to do with it and refused to allow her to explore her pre-existing health condition, so it wasn't only the do nothing approach with my sister, it was also a block any and all further investigation approach.  It was heartbreaking to finally figure out tests to be done on her almost two years after neurological symptoms and find so many things out of balance.  And the question begs to be asked why every last pALS that is fighting for their life is having to research around the clock to figure out what they might do.  

Amy is doing what should be happening for every pALS and by time pALS leave BodyScience, they are noticing improvements in strength, swallowing, turning over, etc.  All pALS deserve this.  With Amy's clinic it took 2-3 years of follow-up treatments to reverse ALS in her first ALS patient and it is proof that it can be done by looking at and studying what's wrong with one person at a time.  Indeed, I didn't learn what I know about ALS by looking at population groups, I learned by following my sister's identified health problems and studying those issues.  I lost the most beautiful sister in the world and within one year of studying ALS I was correctly able to predict high galectin-3 in ALS and I am not in the medical field.  It is a hard thing to reconcile.  Amy will make sure your pALS's health issues are properly worked up and will treat issues that are found.  The only thing neurologist have proven on the individual level is that to do nothing is to ensure 100% fatality.  Amy is proving that pALS can feel better, feel stronger and gain function back and it can be done now.    https://www.bodyscience.life/, https://www.facebook.com/groups/1008584079506823

Just a word on stem cells.  They are shown to improve complement, but my criticism is that zero is done looking for infection, and how to help cell metabolism or cellular imbalances, and nutritional deficiencies.  The amino acids and minerals get further out of balance over time and I just don't see how it treats the broken mitochondria or nutritional imbalances.  If stem cells are your choice, I'd recommend Dr Steenblock because he puts attention into looking for infection and trying to treat it and also attempts to improve immunity and work on nutrition.  Stem cells can also be quite dangerous for further along pALS.  I have seen pALS all excited about getting stem cells and gone within days of getting them.

So, complement is innate immunity and it is insane in ALS.  What isn't being research is how complement evasion is playing a role in ALS.  And actually, in the research in general, complement evasion is void in most analysis.  It is easier to see what is there then to know what a microbe may have removed.

I've just listed studies on complement and I believe factor H and C4bp need a much closer look because factor H enables a microbe to escape detection because it looks like "self."  C4 of complement feeds the activation loop which means like a hormone, very tiny amounts create a large response.  Microbes can disable/disolve/breakdown C4bp, which is why I think sometime high C4A shows up because the way C4 is expressed the entire gene is expressed and then it is split so when one of the split products is removed, it turns down complement and the body needs to express more and when this happens enough you end up with higher C4A.  No one is looking at the effect of herv-k that is in C4 and relationship to schizophrenia with higher herv-k in the C4 and that there is massively higher ALS when your have a first degree relative with schizophrenia (I raise my hand as I lost an uncle with schizophrenia.)

I love you Norma and you are forever missed.

Your big sister Deborah

ALS complement research resources:
I will always be grateful to Dr Williams for this video because it is what led me to studying complement and I probably watched it within a couple months of Norma's March 2015 diagnosis.  I was the top of my class in human biology and I'd never heard of complement.  It remains grossly underappreciated in medicine.
https://www.youtube.com/watch?v=Q-kN-lw2QgQ - Dr Jason Williams discussing how what is seen from stem cells in ALS can not be from regenerating neurons because they grow so slow, so it is a discussion about what the stem cells could be secreting to help.
Video points of interest:
3:00 - patients had a quick response, days to weeks, makes no sense as regrowing nerves takes a long time, conclusion, stem cells make substances that inhibit the ALS process.
4:12 - "Intravenous infusion can't make it to the brain, so how is it helping?
5:10 - Harvard University - Teng, animal study, spinal cord produce substances that were protective, but not nerve regeneration.  Stem cells remained close to injection site but there was benefit through the body.
8:57 - TDP43 - involvement, too much, too less (likely too much)
9:39 - When evaluating several different causes of ALS (mSOD1, TDP-43) the common pathway leads to complement, primitive part of immunity, eliminates debris and dead cells.  Complement has gone amok and attacks healthy cells.
10:15 - Standford, William Robinson, complement causes osteoarthritis.
11:00 - Stem cells for ALS and joints show signs of improvement right away for both, similar mechanism?
11:33 - Complement factor C5a contributes to pathology in rat model of ALS, school of biomedical sciences --> inhibit complement
12:00 - Journal of Neuroimmunology, 235 (2011) 104-109.  Complement activation products are elevated in cerebrospinal fluid, spinal cord and motor cortex of patients...  (complement deposits) were detected at day 47, BEFORE the appearance of clinical symptoms.  Still present at day 126 at destruction of neuron in SOD1 G93a mouse model of fALS.
12:30 - complement is elevated in spinal fluid of ALS, incidentally mentioned in an article (not sourced), further evidence
12:55 - illustration of complement mechanism, c3b starts bonding, builds up attacking nerves.
15:48 - Factor H, the body's regulatory mechanism for complement - protects against the damage caused by complement's attack on neurons in ALS.  Stem cells produce factor H.
16:37 - Factor H inhibited by NSAIDS
17:13 - Illustration for factor H
18:20 - Why do some benefit when others do not? (factor H regulation components come from liver, not treated, also, no idea where I read something to make that conclusion)

Research cited in video (and wiki links for more information):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409288/ Intravenous Mesenchymal Stem Cells Improve Survival and Motor Function in Experimental Amyotrophic Lateral Sclerosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614245/ Trans-differentiation of the Adipose Tissue-Derived Stem Cells into Neuron-Like Cells Expressing Neurotrophins by Selegiline
https://www.prweb.com/releases/2013/5/prweb10755757.htm Stem Cells from Fat Outperform Those from Bone Marrow in Fighting Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224073/ Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis
https://pubmed.ncbi.nlm.nih.gov/19050293/ The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis
https://www.sciencedirect.com/science/article/pii/S0042682210008135 Complement and viral pathogenesis
https://www.sciencedirect.com/science/article/abs/pii/S0165572811000932 Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis
https://en.wikipedia.org/wiki/Factor_H Factor H
https://medlineplus.gov/genetics/gene/cfh/ CFH gene - complement factor H
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921957/ Complement control protein factor H: the good, the bad, and the inadequate
https://en.wikipedia.org/wiki/Complement_component_3 Complement component 3
https://pubmed.ncbi.nlm.nih.gov/22519910/ The advent of AAV9 expands applications for brain and spinal cord gene delivery
https://www.nature.com/articles/gt2012101 Global CNS gene delivery and evasion of anti-AAV-neutralizing antibodies by intrathecal AAV administration in non-human primates
https://pubmed.ncbi.nlm.nih.gov/9159721/ A dose-ranging study of selegiline in patients with Parkinson's disease: effect of platelet monoamine oxidase activity
https://en.wikipedia.org/wiki/Selegiline Selegiline

Other research related to complement and ALS:
https://patents.google.com/patent/US6805857 Method of modulating factor D, factor H and CD4 cell immune response with a polystyrene sulfonate, alginate, and saline infusion solution
https://patents.google.com/patent/EP0854150B1/en?oq=factor+h Inhibition of binding of complement factor H
https://pubmed.ncbi.nlm.nih.gov/20843825/ An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD)
https://pubmed.ncbi.nlm.nih.gov/24053733/ Prevalence of Epstein-Barr Virus in a population of patients with inflammatory bowel disease: a prospective cohort study
https://journals.asm.org/doi/full/10.1128/jvi.79.17.11128-11134.2005 Epstein-Barr Virus Can Establish Infection in the Absence of a Classical Memory B-Cell Population (CD40?)
https://pubmed.ncbi.nlm.nih.gov/20348957/ From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis
https://www.sciencedirect.com/science/article/pii/S0169409X18303089 Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity and beyond
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233638/ Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis
https://cdmrp.army.mil/alsrp/research_highlights/19perrin_highlight Amyotrophic Lateral Sclerosis (ALS) Treatment, AT-1501, Enters Clinical Trial (CD40L treatment)

https://pubmed.ncbi.nlm.nih.gov/16982911/ Galectin-3 induces death of Candida species expressing specific β-1, 2-linked mannans
https://www.jimmunol.org/content/181/4/2781 Galectin-3 is a negative regulator of lipopolysaccharide-mediated inflammation
https://pubmed.ncbi.nlm.nih.gov/20698585/ Galectin-3 is a candidate biomarker for amyotrophic lateral sclerosis: discovery by a proteomics approach
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489809/ Deletion of galectin‐3 exacerbates microglial activation and accelerates disease progression and demise in a SOD1 G93A mouse model of amyotrophic lateral sclerosis (Who have thought when you remove a part of immunity to fungal infection...)

More complement, fungal, viral, various microbes, and role in ALS:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1307025/ Insight into a conserved lifestyle: protein-carbohydrate adhesion strategies of vector-borne pathogens
https://pubmed.ncbi.nlm.nih.gov/23809232/ Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans
https://www.meta.org/papers/immune-evasion-of-the-human-pathogenic-yeast/19850343 Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a Factor H, FHL-1 and plasminogen binding surface protein
https://pubmed.ncbi.nlm.nih.gov/25088819/ Metabolism impacts upon Candida immunogenicity and pathogenicity at multiple levels.
https://pubmed.ncbi.nlm.nih.gov/25612733/ Bimodal Influence of Vitamin D in Host Response to Systemic Candida Infection—Vitamin D Dose Matters.
https://pubmed.ncbi.nlm.nih.gov/26096806 Vitamin D is not a protective factor in ALS
https://pubmed.ncbi.nlm.nih.gov/12244181/ Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC98369/ Complement evasion by Borrelia burgdorferi: serum-resistant strains promote C3b inactivation.
https://pubmed.ncbi.nlm.nih.gov/19140878/ Complement split products C3a and C4a in chronic Lyme disease. (split products are likely not as expected because of borrelia taking one out.)
https://www.sciencedirect.com/science/article/abs/pii/S1471492212001997 Complement evasion by Borrelia burgdorferi: it takes three to tango.  (the co-infections with borrelia ensure complement is crippled)
https://pubmed.ncbi.nlm.nih.gov/26808924 Borrelia burgdorferi BBK32 Inhibits the Classical Pathway by Blocking Activation of the C1 Complement Complex.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170916/ A tick mannose-binding lectin inhibits the vertebrate complement cascade to enhance transmission of the Lyme disease agent (increase mannose so tick binds inactive targets?)
https://pubmed.ncbi.nlm.nih.gov/25816986/ More than just immune evasion: Hijacking complement by Plasmodium falciparum (borrelia co-infection babesia is similar to malaria)
https://www.sciencedirect.com/science/article/abs/pii/S0074774216301416 Chapter Seven - Toxoplasma gondii—A Gastrointestinal Pathogen Associated with Human Brain Diseases
https://selfhack.com/blog/dr-gundry-turning-off-autoimmunity-with-a-lectin-avoidance-diet/ Dr. Steven Gundry: Stop Autoimmunity with a Lectin-Free Diet
https://pubmed.ncbi.nlm.nih.gov/21134964/ Native properdin binds to Chlamydia pneumoniae and promotes complement activation (properdin and factor H balance each other)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0027546 Functional recruitment of human complement inhibitor C4B-binding protein to outer membrane protein Rck of Salmonella
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654503/ Immune evasion by acquisition of complement inhibitors: the mould Aspergillus binds both factor H and C4b binding protein
https://pubmed.ncbi.nlm.nih.gov/19608625/ Acquisition of factor H by a novel surface protein on group B Streptococcus promotes complement degradation.
https://jamanetwork.com/journals/jamaneurology/article-abstract/581136 A cluster of amyotrophic lateral sclerosis (Mold exposure?  High level of herv-k repeats in C4bp? 1st degree relative with schizophrenia?)
https://pubmed.ncbi.nlm.nih.gov/7810588/ Elevated risks for amyotrophic lateral sclerosis and blood disorders in Ashkenazi schizophrenic pedigrees suggest new candidate genes in schizophrenia (15,000% increase - no words to express the degree to which it says "look here," but there is zero research path from here.) 
https://pubmed.ncbi.nlm.nih.gov/27617889/ Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel (4x the rate of ALS, reinforces the "look here" message)
https://www.nature.com/articles/nature16549  Schizophrenia risk from complex variation of complement component 4 (C4bp is a split product of C4, and the higher the level of herv-k repeats in the C4, the more schizophrenia risk)
https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.410150610 Tissue culture demyelination by normal human serum ( C4 or C6 deficiency induce demyelination - complement evasion of C4bp would reduce C4)
https://www.ncbi.nlm.nih.gov/gene/720 C4A complement C4A (deficiency associated with systemic lupus erythematosus and type I diabetes, produced in the liver)
https://pubmed.ncbi.nlm.nih.gov/26424568/ Human endogenous retrovirus-K contributes to motor neuron disease. (There are many different herv-k in the body.  The C4 herv-k is poorly studied.)
https://pubmed.ncbi.nlm.nih.gov/19174564/ Structural insights into TDP-43 in nucleic-acid binding and domain interactions (TDP-43 was discovered because it went up in response to HIV, making me believe it plays a role in controlling viruses.)
https://n.neurology.org/content/84/14_Supplement/I4-1A Activation of HERV-K and response to antiretroviral therapy in patients with HIV infection and motor neuron disease 
https://academic.oup.com/labmed/article/39/5/291/2504709 Chronic bacterial and viral infections in neurodegenerative and neurobehavioral diseases.
https://pubmed.ncbi.nlm.nih.gov/26418545/ Staphylococcus aureus protects its immune-evasion proteins against degradation by neutrophil serine proteases
https://pubmed.ncbi.nlm.nih.gov/24311574/ Staphylococcus aureus thiaminase II: oligomerization warrants proteolytic protection against serine proteases
https://www.ijbs.com/v11p0546.htm Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis
https://pubmed.ncbi.nlm.nih.gov/25847918/ Leaky intestine and impaired microbiome in an amyotrophic lateral sclerosis mouse model. (Dysregulation of alpha defensin 5 likely means there is increased demand for aromatic amino acids and a very different demand for minerals then when normal, something the body is designed to deal with short term only.)
https://pubmed.ncbi.nlm.nih.gov/19050293/ The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis
https://www.sciencedirect.com/science/article/abs/pii/S0006291X06003317 Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson’s disease
https://pubmed.ncbi.nlm.nih.gov/8021681/ Increased concentration of C4d complement protein in CSF in amyotrophic lateral sclerosis
https://pubmed.ncbi.nlm.nih.gov/26928464/ Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis (This part of adaptive immunity.)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782700/ Targeting angiogenin in therapy of amyotrophic lateral sclerosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774800/ Paneth cells: their role in innate immunity and inflammatory disease.
https://pubmed.ncbi.nlm.nih.gov/26489954/ Complement activation, regulation, and molecular basis for complement‐related diseases
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030870/ Factor h: a complement regulator in health and disease, and a mediator of cellular interactions
https://pubmed.ncbi.nlm.nih.gov/16571820/ Herpes simplex virus type 1 and 2 glycoprotein C prevents complement-mediated neutralization induced by natural immunoglobulin M antibody
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC189073/ Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. (TDP-43 discovered, "TDP-43 is a potent inhibitor of HIV-1 gene expression" - inhibits retroviruses?)
https://pubmed.ncbi.nlm.nih.gov/27782329/ Complement in removal of the dead - balancing inflammation (broken because of lack of ATP energy?)
https://www.sciencedirect.com/science/article/pii/S0925443913002986 Amino Acids as biomarkers in the SOD1 G93A mouse model of ALS
https://pubmed.ncbi.nlm.nih.gov/25860609/ Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
https://pubmed.ncbi.nlm.nih.gov/26241678/ Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model.  (malnutrition with dysbiosis)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257059/ Identification of a central role for complement in osteoarthritis (C4A markedly higher, C4bp lower - these are split products that suggest complement evasion)
https://www.nature.com/articles/s41396-021-01123-5 Altered metabolome and microbiome features provide clues in understanding irritable bowel syndrome and depression comorbidity (poor gut health dysrupts tryptophan metabolism and reduces serotonin)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954194/ Platelet Serotonin Level Predicts Survival in Amyotrophic Lateral Sclerosis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499429/ Elevated acute phase proteins reflect peripheral inflammation and disease severity in patients with amyotrophic lateral sclerosis (high APP associated with faster progression.  APP are high in aromatic amino acids, like tryptophan, so would lower serotonin.)
https://www.sciencedirect.com/science/article/abs/pii/S1549963420301039 Raman spectroscopy reveals biochemical differences in plasma derived extracellular vesicles from sporadic Amyotrophic Lateral Sclerosis patients (low aromatic amino acids in extracellular vesicles)
https://www.youtube.com/watch?v=Wf8sw3n7xrE Vaccine Safety Conference Session 13 - Dr. Yehuda Shoenfeld (silicon implant - developed lupus "antinuclear antibody titers decreased from 1/1280 to 1/160, C4 and raised angiotensin converting enzyme normalized.)
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-016-0538-2 Complement activation at the motor end-plates in amyotrophic lateral sclerosis (this happens BEFORE motor neuron involvement)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672214/ Microarray Analysis of the Cellular Pathways Involved in the Adaptation to and Progression of Motor Neuron Injury in the SOD1 G93A Mouse Model of Familial ALS
https://www.youtube.com/watch?v=chQluxF9cY0 The Complement System Made Simple (best explanation of how complement works)
https://www.wikipathways.org/index.php/Pathway:WP545 Complement activation
https://pubmed.ncbi.nlm.nih.gov/25065463/ Bacteria under stress by complement and coagulation

This wonderful table on complement evasion is from the work done by Dr Lambis' group.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814840/ Complement evasion by human pathogens
Supplemental table 1.
Complement proteins that are inhibited via proteolysis by the pathogen
PaE, AprA
Pseudomonas aeruginosa
HRgpA, RgpB, Kgp
Porphyromonas gingivalis
Tannerella forsythia
PaE, AprA
Pseudomonas aeruginosa
PaE, AprA
HRgpA, RgpB, Kgp, PrtH
Pseudomonas aeruginosa
Porphyromonas gingivalis
Tannerella forsythia
Prevotella intermedia
Staphylococcus aureus
Streptococcus pyogenes
Enterococcus faecalis
HRgpA, RgpB, Kgp
Porphyromonas gingivalis
Tannerella forsythia
Aeromonas sobria
C5a peptidase ScpA
C5a peptidase SpcB
Group A Streptococci
Group B Streptococci
Serratia marcescens
C3, C4b
Staphylococcus aureus
Pseudomonas aeruginosa
Cronobacter sakazakii
Bacillus anthracis
Complement proteins that are modulated by the pathogen
SpA, Sbi
40kD porin
Staphylococcus aureus
Aeromonas salmonicida
C3 convertase
C3b & C3 convertase
Moraxella catarrhalis
Staphylococcus aureus
Staphylococcus aureus
C5 convertase
Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus
O-chain variation
Capsule expression
APS layer
O-chain variation
O-chain variation
O-chain variation, Rck
O-chain variation
YadA, Ail
Group A Streptococci
Escherichia coli
Borrelia burgdorferi
Klebsiella pneumonia
Neisseria meningitides

Porphyromonas gingivalis
Salmonella minnesota
Salmonella montevideo
Salmonella typhimurium
Shigella flexneri
Yersinia enterocolitica
(Hallström et al. 2013)
(Merino et al. 1992)
(Sjölinder et al. 2008)
(Schneider et al. 2007)
(Slaney et al. 2006)
(Joiner et al. 1982)
(Grossman et al. 1987)
(Murray et al. 2005), (Heffernan et al. 1992)
(Hong & Payne 1997)
(Pilz et al. 1992)(Bliska and Falkow 1992)
Complement regulatory proteins that are acquired by the pathogen
Escherichia coli
Bordetella pertussis
Por1A, Por1B
UspA1, UspA2
43kD receptor
YadA, Ail
Group A Streptococci
Streptococcus pyogenes
Streptococcus pneumonia
Neisseria gonorrrheae
Mycoplasma catarrhalis
Escherichia coli
Bordetella pertussis
Borrelia burgdorferi
Yersinia enterolitica
Porphyromonas gingivalis
Borrelia burgdorferi
Borrelia garinii
(Haupt et al.2007
(Van Burgel et al. 2010))
M protein
Beta protein
Hic, CbpA
Spe B, Emm18
Se18.9 protein
Por1A, Por1B
YadA, Ail
Gp120, gp41
Group A Streptococci
Group B Streptococci
Streptococcus pneumonia
Streptococcus pyogenes
Streptococcus equi
Neisseria gonorrrheae
Yersinia enterolitica
Acinetobacter baumanii
Borrelia burgdorferi,  Borrelia spirochete
Leptospira interrogans
Treponema denticola
Staphylococcus aureus
West Nile

Simian virus 5, mumps virus, NDV, HCMV, MCMV, HHV-7, SIV, HIV-1

HIV-1, SIV, HTLV-1, NDV, HCMV, Vaccinia

Protein E, Hsf
Haemophilus influenzae
Haemophilus ducreyi
Moraxella catarrhalis
Neisseria gonorrhoeae
Neisseria meningitides
Rickettsia conorii
(Leduc et al. 2009)
(Attia et al. 2006), (Singh et al. 2010)
(Duensing and Putten , 1998)
(Griffiths et al.2011), (Sa E Cunha et al.2010)
(Riley et al. 2013)

Helicobacter pylori, Escherichia coli, HIV-1, SIV, HTLV-1, HCMV, Vaccinia, Influenza, HCV

Borrelia burgdorferi

Supplemental Table 1. Overview of bacterial and viral complement evasion tactics. Many bacteria and viruses evade complement by inhibiting complement activity either by proteolysis of complement factors or by modulating their functionality. Pathogens may also evade complement activation through the acquisition of complement regulatory proteins. These complement regulatory factors can be acquired from the host as a protein (e.g. during budding from the cell membrane) or as a gene during its evolution. In addition, proteins of the pathogen may evolve to mimick the function of host CRPs. HCMV = Human cytomegalovirus, HCV = hepatitis C virus, HHV = human herpes virus, HIV = human immunodeficiency virus, HSV = herpes simplex virus, HTLV = human T-cell lymphotropic virus, KSHV = Kaposi's sarcoma associated herpes virus, MCMV = murine cytomegalovirus, NDV = Newcastle disease virus, RRV = Ross river virus, SIV = simian immunodeficiency virus.

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