Mannose-binding Lectin Inflamation

[greeno]

MBL looks like a good place to start some discussions. I encourage everyone to read this article on MBL to get a good understanding on how inflammation starts.

http://www.bio.davidson.edu/courses/immunology/Students/spring2006/Mohr/MBL.html

This is the important bit:

“The MBL2 gene encodes mannose-binding lectin (MBL) that is secreted by the liver into the bloodstream (Ohlenschlaeger et al., 2004). Although serum levels of MBL are normally rather low (1500 micrograms/litre), MBL has a crucial role in innate immunity (Turner, 1998). The frequency of this deficiency due to mutations of the MBL2 gene in the general population has been estimated to be between 5 and 10% ( Turner, 1991 ). MBL deficiency arising from mutations and promoter polymorphisms in the MBL2 has been associated with increased risk, severity, and frequency of infections and autoimmunity (Flemming, et. al., 2004).
 Although most individuals with MBL deficiency are healthy, they have an increased susceptibility to certain illnesses. The deficiency has been reported to be particularly common in infants with recurrent respiratory tract infection, otitis media, and chronic diarrhea. The low levels of MBL in young children with recurrent infections suggest that the MB-lectin pathway is important during the interval between the loss of passively acquired maternal antibody and the acquisition of a mature immunologic repertoire (Summerfield et al., 1997).
MBL deficiency is also associated with non-infectious diseases in adults including systemic lupus erythematosus, rheumatoid arthritis, cystic fibrosis and common variable immunodeficiency. MBL deficiency increases susceptibility to infectious disease. One study that found a significantly higher number of HIV-infected homosexual males were homozygous for variant MBL2 alleles than were high-risk homosexual controls or healthy controls. Although no significant association was found in progression from infection to clinical AIDS, there was a significantly shorter mean survival time after AIDS diagnosis in men carrying variant MBL2 alleles and those with low serum MBL. The increased risks may be associated with increased susceptibility to coinfections (Garred et.al, 1997).  MBL-deficiency also poses a problem for other immuno-compromised individuals, such as cancer patients undergoing chemotherapy. In these patients, there was a strong correlation between MBL-deficiency and the occurrence of clinically significant infections. In addition, studies of cystic fibrosis patients found that MBL-deficient patients have a life expectancy 8-years shorter than MBL sufficient individuals, due to increased bacterial colonization of the lung (Trevisiol, 2005).
If MBL is involved in clearing away bacteria and other pathogens, why is MBL deficiency associated with autoimmune diseases such as lupus and rheumatoid arthritis? The immune system has redundant pathways that all have the same function so that if one is not working well, the immune system can still operate. For example, the classical, MB-lectin, and alternative pathway all make a C3 convertase which leads to oposinzation of pathogens, recruitment of inflammatory cells, and killing of pathogens (see Fig. 4). If the MB-lectin pathway is not working well due to MBL deficiency, the immune system compensates by increasing activation via the other pathways. Most notable is the increase in antibody concentration, used in the classical pathway. Studies have shown an increase in serum levels of IgM antibody concentrations in MBL deficient patients with rheumatoid arthritis. The more antibody, the higher the chance that some antibody will be self-reactive, which is what happens in arthritis( Jacobsen, 2001).

1. If MBL is defective in Inflamatory disease patients( mutations and promoter polymorphisms in the MBL2), then couldn't it be the case that the defective lectin can not attach to the pathogen i.e fermentans, or Candida?

2. If dective MBL is like a trigger for inflamation, and isn't really doing anything good, then couldn't we attempt to clear it out of the system with D-Mannose?

http://www.waterfall-d-mannose.com

http://en.wikipedia.org/wiki/Mannose.

3. Lot's of stuff to take in here, but it all kind of fits together with Heredity, pathogens. Fit's in with my theory that us poor unfortunates can not get away with challenging our GUT strength, since once it is compromised, we don't have the right immune response (functioning MBL) to hold back the tide of bad bacteria. This would explain why we can not get of Minocin, as we are in a constant battle against bacteria of the sugar feeding variety, and why it can take so long for Minocin to work for some hmmm.

4. Although not mainstream, we need something powerful to take on the bad guy's like MMS (Chlorine Dioxide). We need a MBL replacement therapy? This would explain why Minocin works well in early cases of RA, since GUT compromise is only starting to take place, and the bad bacteria is only just starting to creep into the blood stream.    
   

[Author]

Posts