IBD Less Common in Sunny States

I've blogged about this before, but there was a recent study that revealed that people who live in sunnier regions of the United States are less likely to develop IBD. It confirms previous research conducted in Europe that generated the similar results. The study followed over 200k participants that began the study without symptoms of IBD.

The basic explanation for this is Vitamin D. There's a strong role for Vitamin D in the immune response and IBD patients (including myself) often have low Vitamin D levels. So stop postponing that vacation to Hawaii already!

Here's an excerpt:

"A leading explanation for this north-south gradient in the risk of ulcerative colitis and Crohn's disease may be differences in exposure to sunlight, or UVB radiation, which is generally greater in southern latitudes," wrote Dr. Hamed Khalili, of Massachusetts General Hospital in Boston, and colleagues.

"UV radiation is the greatest environmental determinant of plasma vitamin D, and there is substantial experimental data supporting a role for vitamin D in the innate immunity and regulation of inflammatory response," they noted.

Key proteins that cause Celiac disease discovered

Saw a few articles (ABC News, Geek System) about a study in Melbourne that identified several proteins that cause Celiac Disease. There are apparently three or four different protein fragments that can trigger the disease. Celiac is caused due to an allergic reaction to these proteins. The researchers hope to create an immunotherapy treatment where patients can build up immunity to those proteins. Very interesting development and certainly gives hope for the more than 2 million people in the US that suffer from the disease.

Here's an excerpt about the potential immunotherapy treatment:

Professor Anderson says the findings are being used to develop a new class of drugs, called peptide-based immunotherapy.

This involves injecting patients with a small amount of the toxic peptides to "desensitise" their body to them.

The researchers say the first phase of trials of the therapy to assess safety and tolerability were completed in June, and final results are expected in coming months.

Definitely great news.

Controversial treatment for MS - and another angle for research of IBD

I don't know much about multiple sclerosis, but I see articles about it all the time as I monitor news about autoimmune diseases. I came across an article about a controversial treatment for MS that a person in Britain couldn't get because it hasn't been officially sanctioned by the government yet via clinical trials. For a person with IBD, I found the treatment less interesting than what it suggests about the potential cause of the disease.

Here's a really short excerpt just to give you an idea:

In 2005, Zamboni’s wife Elena was diagnosed with MS and he embarked on a mission to find out everything about it, from poring over medical literature dating back 100 years or more, to using state-of-the-art body-imaging techniques.

His conclusion was that this wasn’t only an autoimmune disease, but also a vascular one, caused by restricted, blocked, malformed or twisted veins in the trunk and neck. A small study showed that 90 per cent of his patients had venous obstruction. He named the condition chronic cerebrospinal venous insufficiency (CCSVI) and went further, postulating that an excess of iron, which causes inflammation and cell death, was responsible for tipping the immune system out of balance, resulting in MS symptoms.

The treatment was to unblock these twisted or malformed veins (similar to an angioplasty). What I found interesting is that an autoimmune disease, in this case MS, might not just be caused by the environment or genetic susceptibility, it might also include a physical malformation in the body that can be reversed! Might there be something similar with IBD? They should add that to the list of things to research.

UPDATE (8/2/2010): Saw an article in the WSJ about a study that refutes the Zamboni theory regarding jugular vein blockage. Jury is still out I suppose.

Alopecia Areata and Narcolepsy both confirmed as autoimmune diseases

The list of health issues that are being categorized as autoimmune diseases are just stacking up! Saw an article a couple weeks ago that alopecia areata, a disease that causes hair loss and baldness, was caused by an autoimmune response. And a more recent article confirmed that narcolepsy is also autoimmune.

In alopecia areata, they found that some genes which attract killer immune cells are overexpressed in hair follicles. The immune cells attack the follicles and lead to rapid hair loss. In narcolepsy, the body's immune system attacks cells responsible for creating a certain hormone (hypocretin) in people's brains that's responsible for keeping people awake. The lack of hypocretin causes people to randomly and unexpectedly fall asleep.

It's amazing how many health problems are falling under the autoimmune category.

Antibiotics in Infancy Potentially Linked to IBD Risk

A small study showed that there might be an increased risk of IBD for infants that are given antibiotics in their 1st year of life. The study compared 36 children with IBD with 360 children that did not have IBD. 60% of the group with IBD had been given antibiotics compared to only 40% for the non-IBD group. The difference was even more pronounced for boys than girls. The study suggests a possible root cause or causative agent in the development of the disease. But again, this was a very small study, so this just suggests areas for additional research.

Discovery Prompts New Theory on Cause of Autoimmune Diseases

Saw an article in ScienceDaily about a new theory on the cause of autoimmune diseases, including Crohn's Disease. Researchers discovered a protein (or peptide) fragment that's capable of causing diabetes in mice. The basic hypothesis is that the unusual introduction of these peptides allows errant T-cells to escape the thymus and make there way to other parts of the body where they initiate immune responses associated with autoimmune diseases. These errant T-cells that are autoreactive (or that react to your body's own cells) are normally deleted by the immune system. However, the introduction of these rare peptides causes the deletion procedure to not work properly.

Here's an excerpt:

In the April 23, 2010, issue ofImmunity, Drs. Brian Stadinski, John Kappler and George Eisenbarth propose that the unusual and rare presentation of protein fragments (peptides) to the immune system allows autoreactive T cells to escape the thymus and trigger autoimmune disease. The findings could lead to a new strategy for preventing type 1 diabetes.

"The immune system normally deletes dangerous, autoreactive T cells that recognize 'self' peptides, which are a normal part of the organism," said Dr. Kappler, Professor of Immunology at National Jewish Health. "We believe autoreactive T cells in diabetes and other autoimmune diseases escape destruction in the thymus because they never see these poorly presented peptides there. But the T cells do encounter those peptides elsewhere in the body and trigger an autoimmune attack."

Pretty fascinating if the theory is correct. It could also suggest very new areas of research for treatment options.

Genetic Variation Not the Only Cause of Crohn's Disease

Saw an article that commented on a recent study of Danish people and thought it was interesting. The basic conclusion was that the NOD2/CARD15 gene variations previously considered a marker for Crohn's Disease actually do not have a statistically significant association with the disease ... at least for the Danish population. This certainly runs counter to previous studies.

Here's an excerpt:

The study, was conducted to estimate the likelihood that three particular genetic variants in the NOD2/CARD15 gene are related to the risk Crohn disease in the general population.

The population-based study genotyped 43 596 Danish people followed between January 1976 and July 2007. Using a logistic regression model (used to predict the probability of an occurrence) physicians estimated the risk of Crohn disease in the general population.

"Surprisingly, we found no statistically significant association between NOD2/CARD15 genetic variants and Crohn disease in either of the two general population studies that we analyzed, which suggests a low penetrance of the genetic variants in the European general population," write Dr. Børge G. Nordestgaard, Herlev Hospital, University of Copenhagen, Denmark and coauthors. (Penetrance is the degree to which the gene causes the disease.)

The authors conclude that the penetrance of NO2D/CARD15 genetic variants in relation to risk of Crohn for the Danish population was lower than might have been expected from previous European case-control studies. This should be considered when advising healthy individuals in whom these genetic variants are discovered.

What might this mean? Does this mean that genetic variations do not play a role in Crohn's Disease. Not necessarily. More likely it means that there are many contributing factors and many possible causes - not just one genetic variation. Another excerpt from the note:

In a related commentary http://www.cmaj.ca/embargo/cmaj100300.pdf, Dr. Katherine A. Siminovitch and coauthors write that these research findings reinforce the fact that common diseases have many causes and that in these diseases, the effect of any single gene variant on risk is usually small. This underscores the current challenge in realizing the potential of personalized medicine (use of an individual's specific information to select or optimize preventive care and therapy).

It'll be interesting to see how the research community comments on this in relation to previous studies.

TRPV2 Protein Trips Up Germs

Another article on proteins related to the immune response. TRPV2 allows macrophages to get a better grip on bacteria, allowing the immune response to be more effective. There's no direct relationship found at this point with autoimmune diseases like Crohn's, but you never know. So thought I'd post it.

Here's an excerpt:

Citing the fact that TRPV2 is important not only in helping macrophages to bind to germs, but also in clearing bacterial infection, Caterina noted its potential as a useful drug target. And in cases of autoimmune diseases -- arthritis, lupus and asthma, for example -- it's possible that the inhibition of TRPV2 might help pull back an overactive immune system.

"We think there are going to be a lot of implications beyond just prevention of infectious diseases where this research about TRPV2's function in macrophages might be relevant," Link adds. "Macrophages consume cholesterol and contribute to hardening of the arteries. They also clear out debris when nerves are injured so that new nerves can grow through that area."

GM-CSF Protein Appears Key to Intestinal Balance

Saw this article and thought it was interesting. It's about a protein called granulocyte-macrophage colony-stimulating factor (GM-CSF) that helps regulate gut inflammation.

Here's an excerpt:

Reduced levels of the protein — granulocyte-macrophage colony-stimulating factor (GM-CSF) — could be an underlying factor in severe illness caused by pathogens such as E. coli and intestinal inflammation in inflammatory bowel diseases such asCrohn’s disease, the researchers said.

“The gut normally is in a chronic state of low-grade inflammation that is beneficial,” study author Dr. Martin Kagnoff, professor emeritus of medicine and pediatrics at the University of California, San Diego, School of Medicine, said in a university news release.

“This study shows that GM-CSF has a profound influence in the regulation of cells that determine whether the gut lives in peace with this inflammation or becomes severely inflamed during infection,” he said. “Any time that delicate balance is disrupted, all heck can break loose.”

Kagnoff said the findings might help explain why some people with Crohn’s disease benefit from receiving GM-CSF. A greater understanding of the role of GM-CSF in the gut could lead to new treatments based on the protein, he added.