Rheumatoid Arthritis and Fibrin

Chronic inflammation is associated with many diseases and conditions. There are many inflammatory markers that can be measured. Researchers appear to be continually looking to add to the list of makers to use to identifying diseases. C-Reactive Protein is one common but non-specific maker. Fibrinogen is another that some researchers have added to their inflammatory marker list.

A glossary is shown at the end of the article.

Below is a list of common markers that were used in a 2003 study that examined a number of inflammatory markers in association with heart disease. These included:

  • Soluble adhesion molecules (E-selectin, P-selectin, intracellular adhesion molecule-1, vascular cell adhesion molecule-1)
  • Cytokines (Interleukin-1, Interleukin-6, Interleukin-8, Interleukin-10 and tumor necrosis factor)
  • Fibrinogen
  • Serum Amyloid A (SAA)
  • high-sensitive C-Reactive Protein (hs-CRP)
  • White blood cell (WBC ) count

hs-CRP and fibrinogen are the inflammatory markers with the strongest association of the risk of recurrence of cardiovascular disease.[1]

However inflammation is only a moderate indicator of heart disease. Atherosclerotic conditions can occur when hs-CRP is normal (<1 mg/dL). Highest levels of hs-CRP occur with rheumatoid arthritis, systemic lupus erythematosus which have a slightly higher frequency of atherosclerotic events than those without the conditions.[2]


Red blood cells with irregular size and shape. Fibrin is present.

Filaggrin is a protein. Antifilaggrin antibodies (AFA) are a strong indicator of rheumatoid arthritis. A product that is derived from fibrin (deiminated Aα and Bβ fibrinogen chains, if you are really interested) is deposited in the rheumatoid membranes that is a target for the antifilaggrin antibodies. Antibodies are produced by the immune system in response to a foreign invader (an antigen). In this case, it is the fibrinogen derived products.

This shows that fibrinogen is implicated in the inflammation resulting from rheumatoid arthritis but does not show the original cause of the inflammation that caused the increase in fibrinogen and fibrin in the first place.

Rheumatoid arthritis is strongly associated with urinary tract infections. This is consistent with the observation that rheumatoid arthritis occurs much more frequently in women.

The majority of urinary tract infections are caused by Escherichia coli (E. coli) bacteria followed by bacteria of the Proteus genus.

There is evidence that Proteus bacteria is also involved with rheumatoid arthritis.[3]

An amino acid sequence in a protein in Proteus is similar to a sequence found in collagen. Collagen is the most abundant proteins found in mammals and is the main component of connective tissue. It is found in fibrous tissues such as tendons, ligaments, skin, cartilage and bones as well as other organs. It is cartilage and bones that are affected by rheumatoid arthritis.

So those suffering from rheumatoid arthritis not only need to contend with the inflammation that results from autoimmune response to Proteus, they also are subjected to the immune response to products of the initial immune response.


Red blood cells of regular size and shape. Fibrin is absent.

In a 2013 study, one single high-fat meal increased the levels of the two inflammatory markers that were measured: Interleukin 6 (IL-6); and tumor necrosis factor (TNF-ɑ) with a maximum increase occurring 8 hours after eating. By this time, most people will have consumed their next high-fat meal. [4]

Another study from 2006 showed that when women reduced their intake of fat from 35% to 15%, it resulted in a significant decrease in inflammation markers over a 12 month period. Inflammation markers measured were C-Reactive Protein, HDL Serum Amyloid A and Interleukin 6. As well as a significant decrease in weight (mean 5.9 kg) and BMI (mean 2.3), there was a significant reduction in two of the markers: C-Reactive Protein and LDL Serum Amyloid A.[5]

A whole-food, plant-based diet is optimal for reducing inflammation. Chronic inflammation can be indicated by raised fibrinogen and fibrin which can result in debilitating symptoms. Levels of bilirubin higher than the reference range indicate sub-optimal liver function. Chinese herbs can be of benefit to reduce inflammation.[6] [7] [8]

Fibrin
A fibrous protein that is involved in the clotting of blood. Fibrin forms a mesh of long insoluble strands that covers the wound. Also referred to as Factor 1a.
Thrombin
A protein that involved in the clotting of the blood that causes fibrinogen to join together to form a fibrous mesh to cover a wound.
Fibrinogen
A soluble protein that produced by the liver and is found in the blood. Also known as Factor 1.
Filaggrin
Filament aggregating protein that binds to keratin which is the major protein component of hair, horns, claws, fingernails and skin.
Thrombosis
The formation of a blood clot in a vein or artery. If a blood vessel is injured, platelets (thrombocytes) and fibrin to form a blood clot.
Serum Amyloid A (SAA)
A group of proteins that are associated with HDL particles that are produced by the liver in response to inflammation.
C-reactive protein (CRP)
A protein produced by the liver in response to inflammation.
Soluble cell adhesion molecules
A class of proteins that bind to the surface of cells such as platelets in the inflammatory response.
Interleukins
A group of approximately 50 proteins that are known as signalling proteins. Interleukin 6 is responsible for initiating SAA, CRP and neutrophil production.
White Blood Cells (WBC)
Cells of the immune system that protect the body against foreign invaders (antigens). The main types of cells are neutrophils, eosinophils, basophils, lymphocytes and monocytes. Also called leucocytes.
Neutrophils
A white blood cell that is the first to arrive at the site of an infection. Neutrophils help fight infection by ingesting microorganisms and releasing enzymes that kill the microorganisms.
Antibody
A protein that is produced in response to a specific foreign body (an antigen). There are 5 classes of antibodies: IgA; IgD; IgE; IgG; IgG. The antigens may be bacteria, viruses, foreign proteins, carbohydrates or other substances that has been recognised sa foreign. The antibody is like a jigsaw piece that joins with the matching antigen. The immune system removes the combined antigen-antibody complex (or immune complex) in a number of different ways. At times, the new immune complex can become an antigen (or foreign body).
Bilirubin
A product of the breakdown of haemoglobin which occurs when red blood cells are broken down in the liver. It is responsible for the yellow colour of the skin in jaundice. High levels in the blood can indicate liver dysfunction. For several days after birth, bilirubin is much higher than in adults.

Related articles

Rheumatoid arthritis – an autoimmune condition

Footnotes

  1. Pearson, T. A. (2003) Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: A Statement for Healthcare Professionals From the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 107 (3), 499–511.
  2. Roberts, W. C. (2010) It’s the cholesterol, stupid! American Journal of Cardiology. 106 (9), 57–73.
  3. Ebringer, A. (2009) Rheumatoid arthritis is caused by Proteus: The molecular mimicry theory and Karl Popper. Frontiers in Bioscience. E1 (2), 577–586.
  4. Miglio, C. et al. (2013) Antioxidant and inflammatory response following high-fat meal consumption in overweight subjects. European Journal of Nutrition. 52 (3), 1107–1114.
  5. Kasim-Karakas, S. E. et al. (2006) Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects of energy intake. The American Journal of Clinical Nutrition. 83 (4), 774–779.
  6. Chan, E. (1993) Displacement of Bilirubin from Albumin by Berberine. Neonatology. 63 (4), 201–208.
  7. Wang, B. (2000) Treatment of chronic liver diseases with traditional Chinese medicine. Journal of Gastroenterology and Hepatology. 15E67–E70.
  8. Huang, W. et al. (2004) A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. Journal of Clinical Investigation. [Online] 113 (1), 137–143.

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