Got this note in my comments file:

"Peter, you may be interested in some recent articles in the April, 2004 issue of the Journal of Allergy and Clinical Immunology re: lectin binding pathway of complement activation and fucosylated proteins that function as selectin ligands. [J Allergy Clin Immunol, Volume 113, Number 4] Regards, Ann Robb, MD�

Thought it would make a good teaching point.

Warning! Technical stuff follows!

Selectins are multifunctional adhesion molecules that mediate the initial interactions between circulating white blood cells and cells lining the blood vessels, usually with the intent of allowing the white blood cells passage through the vessels walls and on into the tissues. They play a role in arteriosclerosis, inflammatory diseases, and metastatic spreading of some cancers. The best understood selectins, E-selectin and P-selectin, show some variation according to ABO type, with higher levels of E-selectin shown to occur in individuals who are type A. The sugar fucose appears to be critical the proper function of selectins. Interestingly, most likely through the interaction of the selectin molecule with variations of the Lewis A (non-secretor) and Lewis X antigens, which are in themselves fucosylated.

In a 1999 study published in the Journal Blood, leukocyte adhesion deficiency type II (LAD II), a rare inherited disorder of fucose metabolism that leads to severe mental retardation and immunodeficiency (caused by the absence of carbohydrate-based selectin ligands on the surface of the white blood cells) was reversed by oral supplementation of fucose, which induced the expression of fucosylated selectin ligands on the patient's white blood cells. During 9 months of treatment, infections and fever disappeared, elevated white blood cell counts returned to normal, and psychomotor capabilities improved.

In short, fucose is important for proper selectin function, proper selectin function is critical for efficient regulation of inflammation --and a host of other metabolic and immune functions.

The Complement System is a part of the immune response that occurs when an antibody comes into contact with the antigen to which it was manufactured. In some instances, such as when a transfusion is mismatched, the antibody-antigen interaction is so lethal that the foreign object is destroyed immediately. More commonly, the antibody-antigen interaction stimulates an ‘effector mechanism' that actually does the dirty work.

There are three pathways to complement activation, though as a student twenty-five years ago, I was taught that there were only two. The two I was taught were referred to as the ‘classic' and ‘alternative' pathways.

The Classic Pathway is the standard way that an antibody-antigen complex stimulates complement, usually by activating a chain reaction resulting in the conversion of a preexisting circulating inactive molecule into a new molecule that coats the membrane of the invader and then itself is converted into another molecule that attacks the membrane of the invader by boring holes in it.

The Alternative Pathway to activating complement is really much like the Classic, except that instead of antigen-antibodies triggering the complement cascade, many bacteria and foreign objects trigger it directly.

Recently, it was discovered that lectins form a unique, third way to activate complement, most notably through the example of a lectin that is found in our blood serum called Manna Binding Protein (MP. Non-secretors appear to have lower levels of complement than secretors.

Put another way, antibodies ‘finger' the target, complement destroys it.

Someone asked about whether celiac disease and blood types have any link. There is a published study that claims a strong link between non-secretor status and celiac disease, and other authors have seen a link between the variations in intestinal alkaline phosphatase seen with the ABO types and celiac.