Lymphocytes, such as the one shown here, include B cells that play a key role in autoimmunity. Image by Triche/National Cancer Institute
Posted on 05/25/2011 2:10:48 PM PDT by neverdem
Carbohydrate activates B cells in skin, connective tissues
Researchers led by HMS Associate Professor of Medicine Julia Wang offer a new, unifying theory on the origins of autoimmune diseases. In two related papers in the May 2011 issue of the American Journal of Pathology, the team outlines a process by which a carbohydrate abundant in skin and connective tissue called dermatan sulfate turns traitorous. The resulting disease may be systemic, as in lupus or rheumatoid arthritis, or localized, as in Type 1 diabetes or Graves’ disease.
Only a tiny subset of molecules in the body are known to have the potential to become autoantigens, targets of an immune system that mistakes “self” as foreign. Immune B cells play a key role by producing autoantibodies to these autoantigens.
In mice, Wang, along with current and former research fellows Jongmin Lee, Ming Yan, Jung-hyun Rho and Michael Roehrl, demonstrate that dermatan sulfate plays a pivotal role in regulating a type of B cell called B-1a. Levels of both dermatan sulfate and B-1a cells are elevated when cell turnover is high, as in wound healing.
The researchers suggest that, when dead cells pile up, dermatan sulfate may help speed the clearing of these cells by the immune system. Dermatan sulfate has a downside, however. When cells with a high affinity for the molecule die, the resulting complexes can become unrecognizable as self. These complexes stimulate the proliferation of B-1a cells and the production of autoantibodies, which in turn mark healthy tissues for destruction. When autoantibodies bind to autoantigens on healthy cells, other autoimmune B cells infiltrate the tissue, and damage ensues.
Lymphocytes, such as the one shown here, include B cells that play a key role in autoimmunity. Image by Triche/National Cancer Institute
In an accompanying patient study, Wang and colleagues Rho, Roehrl, Wei Zhang and Mandakolathur Murali found that the full complement of autoantigens in humans—more than 200—could be classified by their affinity for dermatan sulfate. “It is those molecules that can associate with dermatan sulfate which have a propensity to become autoantigens,” Wang said.
Wang and her coauthors came to their conclusion by an unconventional route. “We did not investigate this in the traditional immunological way, using genetic approaches,” Wang explained, referring to the strategy of tinkering with genes to heighten or dial back certain proteins in B cells or other autoimmune-response components.
Instead, Wang said, “we used immunological, biochemical and proteomic tactics to isolate a common denominator among autoantigens” in cell cultures, in a mouse model, and in humans. With most research focused on proteins, she said, dermatan sulfate has not been an obvious target for study.
Autoimmune diseases “are ripe for a real breakthrough,” said Wang, who with colleagues has begun developing personalized molecular serum testing for patients to help diagnose autoimmune diseases at a more precise molecular level.
“Many therapies target over-reactive B cells,” Wang said. “Now, with a new mechanism for B-1a cell activation in mind, scientists have a chance to disrupt the start of that dangerous process.” —Mary Bates
To learn more, students may contact Julia Wang at julia_wang@rics.bwh.harvard.edu
Human proteins with affinity for dermatan sulfate have the propensity to become autoantigens.
immunology ping
Thye are a suspicious bunch. Never trusted them. Figures a rogue GAG would make all that trouble.
Thank you!
Thanks for the interesting post. I have alopicia, and the doctor has told me that it’s a typr of auto-immune disorder. I wonder if this research will benefit me.
I autoimmuned an ex wife once
An alternate hypothesis would be:
iron loading in the liver reduces HCl secretions in the stomach and eventually in the gut. Deficient HCl in the gut
causes incomplete digestion, huge proteins that resemble pathogens, massive over-growths of alien flora in the gut and absorption of huge proteins into the blood that are mis-identified as pathogens. The immune response would stay on high alert 24/7/365 while attacking the huge food proteins.
The iron in the liver reduces the levels of hydroxylated vitamin d which upregulates the autoimmune pathology.
I hope this research will prove fruitful. I suffer from a few auto-immune disorders. Usually when you have one you get more. They tend to cluster. Sadly.
I like yours better. Enough vitamin D seems to reduce a lot of autoimmune activity, and avoiding grains makes the gut flora more beneficial as well as keeping these large proteins from slipping into the bloodstream. I am going with your hypothesis.
I have at least one auto-immune disease as well, they are testing me for a couple of others as whatever it is, is flaring up with a vengence right now.
I feel like I should be able to understand this, but I don’t. :(
I have been very busy and have not taken time to look into an anti-inflammation diet, but most autoimmune disease have some kind of inflammatory element to them.
I don’t much either, really! All I know is that since we started supplementing with vitamin D around here, no one seems to get sick. Including the little autoimmune things. We don’t have a big autoimmune thing here, thank G-d, but I one of us did, I’d add testing and supplementation of D.
And when you eat grains, especially glutens, they are so hard to digest and they mess up the digestion process in your gut, which takes place because of the gut bacteria, the GOOD ones. Also, when you are eating grains, big particles can get through some of the intestinal holes and these proteins get into your bloodstream and can make you sick or give you neurological problems. Avoiding grains is a very healthy thing to do. Many of the digestive disorders like celiac, IBF, and Crohn’s can be avoided by avoiding glutens or (better) all grains.
Well the two things that have seemed to help me the most have been vitamin D (and B complex) and not eating any wheat. I have been doing that for about a year now. I am not 100% but I would say I am at least 70% better. Enough better that I wouldn’t change back and my Doctor wants me to continue.
I have an inflammatory myopathy.
I’m so sorry for your loss.
So sorry to hear of your husband’s passing. Praying right now for God’s sustaining grace and comfort for you.
I am really sorry to hear that. My condolences.
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