WG & Genetics

[Daggar]

In conversations with Holly's doctors the following 3 always come up as links to WG (auto immune disorders):

1. Infection
2. Antibiotics (prolonged)
3. Genetics (predisposed)

According to them Research resources are stretched to the max with attempts to find safer and more successful treatments. Not enough research into causes has been done -- including genetic factors.

After reading a few studies online I'm leaning toward a possible genetic factor that is triggered by 1 and/or 2. There are too many cases of multiple auto-immune disorders to ignore. The environmental element usually causes 1.

Holly's sister has a skin disorder (lichen sclerosus) that has been linked to the immune system. My wife's family has a history of lupus and MS. There are cases of multiple family inflictions on the WG parent site.

How many have known auto-immune disorders in their extended families?

[Jack]

I think it is only recently that autoimmune diseases have been recognised and it would seem that they are quite common. However, the occurrence of more than one case of Wegener's in a family is almost unknown. I know that when I was first diagnosed there was only one although there seem to be a few more cases now. This is not the case with other autoimmune diseases such as arthritis which have a strong tendency to run in families.
It may be that there is a genetic predisposition towards developing these diseases, but some are just more common than others and Wegener's is one of the very rare forms. Doesn't it make you feel special?

[Daggar]

The genetic studies are hard to find but here's the conclusion of one completed in August/2010 in Sweden.
Conclusion. Relatives of patients with WG are at increased risk of being diagnosed with other autoimmune/inflammatory diseases, indicating shared susceptibility between WG and other auto-immune/inflammatory disease.
Another puzzler is what is classed as an "auto-immune" disorder? Asthma is huge on my side of the family and I just read that some doctors like to class it as an auto-immune disorder while others do not... all very confusing.

[delorisdoe]

autoimmune is very common on my mother side.

a cousin with juvenile diabetes
a cousin with juvenile arthritis
me i am alpha 1 antitrypsin defficient, asthma, wegners.
my brother has psoriasis and something called Devicks-even stranger than wg
mother has psoriasis
father rheumatoid arthritis.

[Daggar]

Interesting German study conclusion:

(2004) performed an extended association screen with 202 microsatellite markers, representing apoptosis-related genes, using pooled DNA of 150 Northern German patients suffering from WG and 100 healthy Northern German controls. Six microsatellite allele patterns were significantly associated with WG. One marker remained significantly associated after multiple corrections. This marker, representing the retinoid X receptor-beta gene (RXRB; 180246), is located in the major histocompatibility complex on chromosome 6p21.3 between the HLA-DPB1 (142858) and DAXX (603186) genes. HLA-DPB1 typing and fine mapping of the region with additional microsatellites and SNPs revealed a strong association of WG with the DPB1*0401 allele (odds ratio of 3.91) compared with controls. In addition, an extended haplotype, DPB1*0401/RXRB03, showed an even stronger association with WG (odds ratio of 6.41).

Mumbo-Jumbo to me but had a friend who studied genetics in University tells me that this would indicate a "connection"..... which once again points to the "not enough research" on the genetic factor as of yet.

[ArlaMo]

As a mother, I hope there is no genetic connection. Wishful thinking, I know...

My sister has fibromyalgia, but that is the only close relative I'm aware of that has an AD.

[JanW]

And I was just reading in the VF newsletter that WG actually doesn't meet all of the 'classic' criterion of an autoimmune disease, so in our lifetime may end up falling out of that classification.

The same article stressed that genetic links had not be found (this for WG in particular, not AI diseases in general).

[Sangye]

At my last appt with Dr Seo I asked him the following:

1) Do you think it's genetic?
No. It's almost never seen in families.

2) Does Wegs occur more often in families with AI diseases?
No. When you look at all the research, the incidence of Wegs in an AI-affected family is the same as in a non-AI affected family.

3) Are the researchers getting any closer to isolating a cause of Wegs?
No. They still have no idea.

We have to be careful when isolating one study's results. The Wegs researchers look at all the studies and can make accurate conclusions.

[Sangye]

And I was just reading in the VF newsletter that WG actually doesn't meet all of the 'classic' criterion of an autoimmune disease, so in our lifetime may end up falling out of that classification.

The same article stressed that genetic links had not be found (this for WG in particular, not AI diseases in general).

Wow, Jan that's really interesting. Can you summarize why it doesn't meet the criteria? (I don't get the newsletter)

[Daggar]

"You have to be "careful" when reviewing one study" -- that's the problem these studies are as "rare" as the disease. WG doesn't occur often in families but AI diseases do and from what I've been told WG is an AI disease. Of the studies that are done in Europe (where most of the WG research has been done) they cannot confirm a definitive genetic connection, however, they cannot rule it out either. Ask the poster on the Weggie Parent site if she feels there isn't a genetic factor -- two daughters and a sister that have WG and polyangitis vasculitis. By ignoring a "possible" genetic connection you limit the chance of finding a possible cure. I'm all for these new studies that are looking into the genetic component -- what are the options? For a doctor to tell you that researchers have "no idea" is disheartening....

I guess the big quesiton is -- If one family member has Lupus... one has Polyangitis Vasculitis.... and another has WG -- would there not be a genetic connection?

The grey area with all this is how often is WG not diagnosed or mis-diagnosed? How often do doctors (not researchers) look beyond the "immediate" family to verify AI diseases? I do not mean to call into question the care Holly's team of doctors have provided but they are so busy with the "treatment" roller coaster they do not have time to ask questions regarding possible causes. So when these doctors are predisposed to the "no idea" way of thinking it is very little wonder why the search for cause or cure have made very little progress.

Sorry for venting!