Endotoxin Binding Protein as a Prognostic marker of Death and Disease

Mostly called Lipopolysaccharide Binding Protein, it is increased in the blood of Astronauts, people infected with Covid19 or on the wrong diet.

I have mentioned Lipopolysaccharide Binding Protein (LPB) in various articles but think we should change its name to align with the Therapeutic Goods Administration and all jab regulatory bodies around the world who report that they have conducted Endotoxin tests on all released batches or accepted certificates from other countries accredited testing labs. But for now, let’s look at some exciting recent discoveries.

Astronauts suffer from elevated LBP

I was interested to find an article¹ where US Space Shuttle and the International Space Station Astronauts were followed after their space voyage with a focus on their circulating LBP.

The abstract states:

This study investigated the ability of the shuttle crew members’ monocytes to respond to gram-negative endotoxin that they could encounter during infections. Blood specimens were collected from 20 crew members and 15 control subjects 10 days before launch, 3 to 4 h after landing, and 15 days after landing and from crew members during their annual medical examination at 6 to 12 months after landing.

When challenged with gram-negative endotoxin, the crew member’s monocytes collected at all three time points produced lower levels of interleukin-6 (IL-6) and IL-1 and higher levels of IL-1ra and IL-8 compared to those of control subjects. Cytokines were assessed by measuring the number of cells positive for intracellular cytokines. These values returned to normal 6 to 12 months after landing, except for IL-1ra, which was still higher (five- to sixfold) than in controls. This phenomenon was accompanied by an increased expression of Toll-like receptor 4 and decreased expression of CD14 on the crew members’ monocytes at all time points.

There were also increased levels of the lipopolysaccharide binding protein in the plasma of the crew members 3 to 4 h and 15 days after landing. This study shows that spaceflight-associated factors (in-flight and preflight) modulate the response of monocytes to gram-negative endotoxins.

An earlier US study of 27 Astronauts found Cytokine disruption.²

Similar studes of Russian Space Station crew and those in a simulator also found disruption of Cytokines.³⁴

Here is what Mouse LPB looks like when its crystal structure is determined and called a conserved two-domain “boomerang” structure,.⁵

The small molecules are 2-acetamido-2-deoxy-beta-D-glucopyranose used during crystallization.⁶

LBP has a molecular weight of about 60 kDa. In Healthy Humans, the level of LBP averaged LBP level was 5.7 μg/mL.⁷

LBP can extract Endotoxin (LPS) monomers from the outer membrane of Gram-negative bacteria and transport them to membrane and soluble forms of CD14 (a 55 kDa glycophosphatidylinositol (GPI)-linked receptor protein that is found on the surface of macrophages, monocytes and neutrophils receptors) promoting the formation of monomeric LPS-CD14 complex that is a critical intermediate in transport of LPS to MD-2/TLR4 and TLR4- dependent inflammatory cell activation.

Addition of small amounts of LBP to cultured macrophages increases by 100-fold the ability of LPS to induce the production of tumor necrosis factor alpha (TNF-α), a potent proinflammatory Cytokine.⁸

LBP acts as an opsonin by enhancing the interaction of LPS with phagocytes.

LBP also delivers LPS to lipoproteins leading to Liver clearance. Patients with Liver Cirrhosis have higher circulating levels of LBP.⁹

The Liver Inflammation due to LBP is independent of Liver Fibrosis.¹⁰

LBP is synthesized by the Liver, Adipose tissue, and Intestinal cells in response to Endotoxin.

“Plasma LBP is used as a better biomarker of plasma LPS than LPS itself due to the short half-life of LPS” (Wikipedia) refers to healthy people keeping their circulating Endotoxin down by binding to LBP.

LBP carries Triacylated Lipoproteins to Toll-like receptor a (TLR1) and TLR2

As well as helping in hitting our TLR4 with endotoxin, other bacterial toxins are transported to TLR1 and TLR2.¹¹

This results in hundreds of different Human diseases.¹²

RhamnoGalacturonan II (RG-II) and LBP

RG-II colocalizes with TLR4, and accessory proteins (CD14 and LBP) are essential for the interaction between RG-II and TLR4 that leads to Interleukin-12 production.¹³

Single Nucleotide Polymorphisms in LBP

As previously mentioned¹⁴¹⁵, individual and racial factors affect the Chromosome 20 expression and effectiveness of LBP against Endotoxin from its gene and the relevance to

• Increased Predisposition to Sepsis in males (p<0.02) but not in female patients and increased LBP in Pregnancy¹⁶

• Infective Endocarditis

• 3-fold increase in the risk of Death prior to discharge, and a 5-fold increase in Mortality risk after Hematopoietic Cell Transplantation.

• Atopy and Asthma involving induced CD4+ Th2 differentiation and overproduction of Immunoglobulin E (IgE) and related Airway Hyperresponsiveness

• Susceptibility to Type 2 Diabetes

• HIV-1/HAART-associated Lipodystrophy Syndrome (HALS).

• Carotid Intima-Media thickness (CIMT) which is a risk for Cardiovascular and Cerebrovascular disease

• Atherosclerosis leading to Myocardial Infarction and Stroke

• Cancers including Colorectal Carcinoma, Gastric Cancer, Glioma,

• Pneumonia and Septic complications

• Inflammation of the Ovary

• Steroid hormone production¹⁷

Obesity and Insulin Resistance

In 2007, it was found by researchers in France that Endotoxin induced LBP is associated with Obesity and Insulin Resistance.¹⁸

In 2016 Moliaro and coworkers¹⁹ found that gut microbiota regulates hepatic expression of LBP through MYD88-dependent signaling. LBP potentiates Endotoxin inhibition of Insulin signaling in vitro and impairs systemic Glucose homeostasis in vivo independent of adiposity.

Alzheimer’s, Parkinsons Diseases and LBP

As mentioned earlier, researchers are investigating supplementation with LBP as a possible treatement for Alzheimer’s Disease.²⁰

LBP reduces Endotoxin Fibrin Clots

As expected, South African researchers who demonstrated Endotoxin in jabs causes Amyloid Fibrin Clots²¹, found that premixing LBP with the Endotoxin to form the bound product reduces Thrombosis.²²

LBP in Covid19 Patients

Zhang and coworkers assembled a database for mining protein dysregulation in patients with COVID-19 and found that LBP was the most frequently reported protein.²³ High-sensitivity C-reactive protein (hs-CRP) correlates with LBP in people suffering long Covid.²⁴

LBP in Multisystem Inflammatory Syndrome in Childhood

Sufferers of Multisystem Inflammatory Syndrome in Childhood (MIS-C) following SARS-CoV-2 infection have high LBP reflecting a defect in intestinal integrity.²⁵

LBP in HIV Patients

Differences were found in HIV patients who had higher²⁶ LBP with implications for Transgender Women on Hormone Therapy, and with different treatment regimes.²⁷

Depression and LBP

German researchers found LBP is a marker for Depression following Covid19 infection.²⁸

Tularemia and Human LBP

Francisella tularensis is the intracellular gram-negative coccobacillus that causes tularemia, and its virulence and infectiousness make it a potential agent of bioterrorism.²⁹ This US Bioweapon knowledge has been used in Fear Marketing of Big Pharma drugs.³⁰

Cardiovascular Disease and LBP

Nice 2020 review.³¹

LBP is a significant and independent predictor of prevalent Coronary Artery Disease (CAD) and male patients with increased levels of LBP had a fivefold increase in CAD prevalence.

LBP was reported as a significant and independent predictor of total and cardiovascular mortality hazard ratio for all-cause mortality [29]. Circulating LBP level is significantly and positively associated with Obesity measures, Insulin Resistance parameters, Glycated Hemoglobin, Fasting Glucose, Fasting Triglycerides, LDL-cholesterol, Systolic Blood Pressure, and Inflammatory parameters while negatively associated with high-density lipoprotein-cholesterol.

circulating LBP is positively associated with carotid intima media thickness (CIMT) in the internal carotid segments and CIMT in overall carotid segments. The findings reveal that serum LBP is a putative risk factor related to atherosclerosis.

Leaky Gut is the trigger for higher LBP

See my earlier article on Gut Dysbiosis induced by jabbing and specially its reference 7 (Guo et al 2013).³² Elevated LBP in Alcoholic Hepatitis is attributed to Leaky Gut.³³ LBP is also elevated in Non-Alcoholic Fatty Liver Disease.³⁴ Not surprisingly a Japanese child with Ulcerative Colitis after Covid19 infection had high LBP.³⁵

High Grain Diet increases LBP

Studies in Cows³⁶ and Horses show that High Grain Diet increases both circulating Endotoxin and LBP response levels.

In Humans, increased dietary fiber intake reduces LBP.³⁷

Human Anti-LBP Antibodies

To further research Human Anti-LBP Antibodies are available from the .Scripps Research Institute and have beeb used by Austrian researchers interested in using killed bacteria as adjuvants.³⁸ Endothelial cells responded much stronger to bacterial ghosts than to Surface layers (S-layers). Bacterial ghosts but not S-layers activated the cells via a LBP-CD14 pathway.

Further References to come

The literature on LBP upregulated by Endotoxin is vast, so I will annoy some readers by circulating now. If I get funding it could be converted from an outline to a comprehensive review or book chapter.

There is much to add about LBP of Astronauts, AUKUS Submariners and others working in confined spaces exposed to each other’s Endotoxin in confined spaces.

1. Indreshpal Kaur, Elizabeth R. Simons, Asha S. Kapadia, C. Mark Ott, and Duane L. Pierson. 2008. Effect of Spaceflight on Ability of Monocytes To Respond to Endotoxins of Gram-Negative Bacteria. CLINICAL AND VACCINE IMMUNOLOGY, Oct. 2008, p. 1523–1528.

2. Brian E. Crucian, Michael L. Cubbage, and Clarence F. Sams. 2000. Altered Cytokine Production by Specific Human Peripheral Blood Cell Subsets Immediately Following Space Flight https://www.liebertpub.com/doi/10.1089/10799900050044741

3. P N Uchakin, O N Uchakina, B V Morukov, I M Larina, N B Bogdanova, m V Mezentseva, B V Tobin, F I Ershov. 2006. The endogenous regulation of the cytokine disbalance in humans subjected to simulated spaceflight environment. Vestn Ross Akad Med Nauk 7:15-20.

4. V B Morukov, M P Rykova, E N Antropova, T A Berendeeva, S A Ponomarev, I M Larina. 2010. Indicators of innate and adaptive immunity of cosmonauts after long-term space flight to international space station. Fiziol Cheloveka 36(3):19-30.

5. https://en.wikipedia.org/wiki/Lipopolysaccharide_binding_protein

6. Jana K. Eckert, Young J. Kim, Jung I. Kim, Kathleen Gurtler, Djin-Ye Oh, Saubashya Sur, Linn Lundvall, Lutz Hamann, Anke van der Ploeg, Peter Pickkers, Evangelos Giamarellos-Bourboulis, Andriy V. Kubarenko, Alexander N. Weber, Michael Kabesch, Oliver Kumpf, Hyun-Jung An, Jie-Oh Lee, and Ralf R. Schumann. 2013. Crystal structure of lipopolysaccharide binding protein. https://www.cell.com/immunity/fulltext/S1074-7613(13)00427-5

7. Regine Landmann, Anne Marie Reber, Sebastiano Sansano, and Werner Zimmerli. 1995. Function of Soluble CD14 in Serum from Patients with Septic Shock. The Journal oflnfectious Diseases 173:661-8.

8. Jeak Ling Ding and Bow Ho. Chapter 9. Endotoxin Detection – from Limulus Amebocyte Lysate to Recombinant Factor C. n X. Wang, P.J. Quinn (eds.), Endotoxins: Structure, Function and Recognition, Subcellular Biochemistry 53:187-208

9. Jack Peter, Oliver Frey, Andreas Stallmach and Tony Bruns. 2013. Attenuated antigen-specific T cell responses in cirrhosis are accompanied by elevated serum interleukin-10 levels and down-regulation of HLA-DR on monocytes. BMC Gastroenterology 13:37

10. Dan Wang, Ania Baghoomian, Zhengyi Zhang, Ya Cui, Emily C. Whang, Xiang Li, Josue Fraga, Rachel Ariana Spellman, Tien S. Dong, Wei Li, Arpana Gupta, Jihane N. Benhammou, and Tamer Sal. 2024. Clin Invest. 134(17):e179752

11. Diana Rose E. Ranoa, Stacy L. Kelley, Richard I. Tapping. 2013. Human lipopolysaccharide binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to toll-like receptor a (TLR1) and TLR2 and enhance formation of the ternary signaling complex. J Biol Chem 288, 9729–9741.

12. TLR2 Diseases caused by Bacterial Lipoprotein in Jabs

13. Sung Nam Park, Kyung Tae Noh, Young-Il Jeong, In Duk Jung, Hyun Kyu Kang, Gil Sun Cha, Su Jung Lee, Jong Keun Seo, Dae Hwan Kang, Tae-Ho Hwang, Eun Kyung Lee, Byungsuk Kwon and Yeong-Min Park. 2013. Rhamnogalacturonan II is a Toll-like receptor 4 agonist that inhibits tumor growth by activating dendritic cell-mediated CD8+ T cells. Experimental & Molecular Medicine (2013) 45, e8; doi:10.1038/emm.2013.14

14. SNPs increase your Risk of Severe Adverse Reaction to Endotoxin in Jabs

15. Leilei Meng, Zichen Song, Anding Liu, Uta Dahmen, Xiao Yang and Haoshu Fang. 2021. Effects of Lipopolysaccharide- Binding Protein (LBP) Single Nucleotide Polymorphism (SNP) in Infections, Inflammatory Diseases, Metabolic Disorders and Cancers. Front. Immunol. 12:681810

16. HOW DOES ESTROGEN ENHANCE ENDOTOXIN TOXICITY? LET ME COUNT THE WAYS

17. Postmenopausal Haemorrhage after mRNA jabs most likely caused by Endotoxin

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20. Alzheimer's Disease caused by Jab Endotoxin

21. Conformal White Fibrin "Clots" are caused by Endotoxin in Jabs

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30. Deaths and Birth Defects from The Wellness Company Fear Kit BigPharma Drugs

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32. Leaky Gut caused by Endotoxin in Jabs

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