Genetics and Mannose-Binding Lectin

Mannose-binding lectin, also known as mannose-binding protein, is involved in the body’s innate defense against infection. Lectin is a general term for a protein that binds to a carbohydrate.  (A lot of what you read about lectins on alternative health blogs is referring to plant lectins, especially those types found in grains, legumes, and nightshades.)

In the body, the lectin pathway is a part of our immune system.  A mannose-binding lectin, therefore, binds to mannose, a simple sugar.  Here’s an example: if a pathogenic bacteria has a sugar called mannose on its surface, the lectin pathway recognizes it and mannose-binding lectin will bind to it.  This activates the body’s immune response to take care of that pathogenic bacteria.

Here is a fifteen-minute video explains the complement system and lectin pathway much better than I can.  https://www.youtube.com/watch?v=FSlghNwPs_M  If you would rather read than watch a video, here is a good overview of complement pathways.

 

Genetically, some people either produce less effective mannose-binding lectin (from now on referred to as MBL) than the rest of the population or they produce less MBL, depending on the variant.  [ref]  Our immune system has lots of backup ways of taking care of pathogens, so for some people, a deficiency of MBL is not a problem and something they may never know that they have.

For people with compromised immune systems, a MBL deficiency can be a problem. [ref] Children with MBL deficiency sometimes have more frequent ear infections or upper respiratory infections. [ref]   A lot of studies have looked at the role of MBL in HIV infections.  MBL can bind to the surface of the HIV virus, so it is being studied to determine if increased MBL affects the rate of progression of HIV.

Like a lot of things in the immune system, there can be both positives and negatives associated with the amount of MBL in the body.   A 2014 mouse study found that MBL is involved in traumatic brain injuries; mice with MBL deficits had fewer sensorimotor deficits that mice with normal MBL. [ref]   So to sum it up in an overly simplified way: a child with lots of ear infections may grow up to have fewer long-term effects from a football concussion.

A 2016 Iranian study found that MBL deficiency was more frequently found in patients with recurrent or severe infections.  The introduction of the study has a very nice overview of MBL deficiency:

“MBL deficiency is defined as an undetectable MBL serum level. Individuals with homozygous variation have plasma concentrations less than 1% of normal levels, heterozygote subjects have about 10% of normal concentration.8 MBL deficiency is considered as the most common inherited immunodeficiency in human, with a frequency of 5% (homozygote) and 30% (heterozygote).9 MBL deficiency is associated with susceptibility to recurrent infections often in the form of upper respiratory, abscess, meningococcal disease and sepsis.8,10 In addition, MBL deficiency is associated with non-infectious diseases including systemic lupus erythematosus, rheumatoid arthritis, cystic fibrosis and common variable immunodeficiency.11 However, most people with subnormal levels of MBL appear to be clinically healthy.2 So far, there has not been established any agreement on the clinical relevance or the treatment of MBL deficiency. ” [ref – click on the pdf to read the whole study]

Genetic variants

The gene MBL2 codes for mannose-binding lectin.

rs1800450 (v.4 and v.5) (minor allele is T) In older studies, the minor allele (T for 23andMe) is known as variant allele B.  Over 20% of Caucasians and Han Chinese are heterozygous for this variant, while around 2-3% are homozygous.    [ref]

  • TT is considered pathogenic for mannose-binding protein deficiency.
  • A 2015 Chinese study found that the A allele was more frequently observed in sepsis cases than in control (OR=2).  It also confirmed that the T allele leads to lower serum levels of MBL in Han Chinese. [ref]
  • Another 2015 study of European ancestry found that MBL2 variants didn’t increase the risk for sepsis in adults who were immune competent. [ref]
  • Studies have found that higher levels of MBL are associated with diabetic nephropathy, and in some populations, the minor allele of rs1800450 is protective against diabetic nephropathy.  [ref]
  • Homozygous and heterozygous variants were more common in bacteremia caused by Staphylococcus aureus (staph infection) [ref]

rs7096206 (v.4 only) (minor allele is G)

  • Lower serum MBL for those with the minor allele.  A 2015 Chinese study found this variant increased the risk of hepatocellular carcinoma by 8x.  [ref]
  • This variant was also found to increase the risk of tuberculosis in nonsmokers exposed to passive smoke and cooking with solid fuel.  [ref]

rs5030737    (v.4 and v.5) (minor allele is A for 23andMe) – also known as codon 52 or allele D in studies.

  • Lower serum MBL for the minor allele. [ref]

rs11003125 (v.4 only) (minor allele is C, with a frequency of around 30%)

  • associated with susceptibility to leprosy [ref] and risk of diabetes [ref]
  • CC genotype had a higher serum level of MBL [ref]

The gene MASP2 codes for mannose-binding protein-associated serine protease 2 which is involved in the MBL pathway.

rs72550870 (v.4 and v.5) (minor allele is C, with a frequency less than 2%)

  • CC is considered pathogenic for MASP2 deficiency [ref]
  • MASP2 deficiency for those who are homozygous [ref]

Mannose-Binding Lectins from outside sources:

Several studies have looked at different Lactobacillus species which can bind to mannose-binding lectins in an effort to prevent HIV and herpes simplex virus.  [ref] Certain L. plantarum species seem to bind to mannose, but it seems that more studies need to be done on the subject.

Sunflower seedlings produce a mannose-binding type lectin.[ref]

Red algae species have been studied for binding to mannose on several types of viruses. [ref] [ref]

More to read:

Antiviral plant Lectins Treat Lethal Viruses. 

 

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