[glenntaj]

--about the extragastric neurological consequences of gluten intolerance:

http://www.medfinds.com/healthnotes....10_04_08_3.cfm

Granted this is only a "pop" communication channel, but given the blind spot a lot of doctors have regarding this, any communication is welcome.

[jccgf]

Thanks!

I believe this is the report referenced:

Lancet Neurol. 2010 Mar;9(3):318-30.
Gluten sensitivity: from gut to brain.
http://www.ncbi.nlm.nih.gov/pubmed/20170845

The article gives a nice review of the various neurological manifestations of gluten sensitivity and some of his more recent findings.

Of particular note is a diagnostic flowchart for a patient with possible neurological manifestion of gluten sensitivity (ataxia, peripheral neuropathy, seizures).

The blood tests to be included are:
antigliadin (AGA IgA and IgG antibodies)
anti-deamidated gliadin (DGP IgA and IgG antibodies)
anti-TG2 (TG2 IgA and IgG antibodies)

If the above are all negative, then additionally test for:
anti-TG6 (TG6 IgA and IgG antibodies... not widely available yet)
HLA DQ2 or DQ8 varients.

"In practice, it is best to do serological tests for both IgA and IgG autoantibodies to TG2 (and, if available, anti-TG6 and anti-TG3) as well as antibodies to gliadin and DGPs."

If any of the tests for gliadin, deamidated gliadin, TG2, or TG6 are positive (IgA or IgG antibodies), or HLA DQ2 or HLA DQ8 are present, then the recommendation is to proceed to biopsy.

If there is enteropathy then a strict gluten free diet is warranted. If there is no enteropathy, testing for IgA deposits against TG on the biopsy should be performed (limited availability). If deposits are found then a strict gluten free diet is warranted.

Anti-TG2 antibodies are deposited in the small bowel mucosa of patients with gluten sensitivity, even in the absence of enteropathy. Furthermore, such deposits have been found in extraintestinal sites, such as muscle and liver. Widespread deposition of transglutaminase antibodies has also been found around blood vessels of the brain in patients with gluten ataxia.

In the case of an uncertain diagnosis, consideration should be given to offering strict gluten free diet particularly if there is no other aetiology and the disease is on a progressive course. Of note, improvement or stabilization does not occur until after a year of strict gluten free diet with serological elimination of antibodies.

SO... Hadjviassiliou's team recommends BOTH the original antigliadin antibody AND the newer anti-deamidated antibody (both IgG and IgA classes). I am happy to have this clarification and direction!

More specifically, they say this:

"Detection of antibodies to deamidated gliadin peptides (DGP) is more specific for detection of coeliac disease than are classic AGA assays. However, unlike autoantibodies to TG2, anti-DGP antibodies can be either IgA or IgG class and not all patients have both. IgG anti-DGP has been reported to have 100% positive predictive value in adults and should therefore be included in the analysis. At present, whether these assays are similarly sensitive for detection of neurological manifestations of gluten sensitivity is not known. Recent evidence suggests that anti-DGP antibodies might be present in only 26% of patients with gluten sensitivity who are negative for TG2 IgA. This finding is consistent with our observation of detectable anti-DGP IgA/IgG in only 25% of patients with ataxia without enteropathy who test positive for autoantibdoies to one or more transglutaminase isozymes.

They also note that IgG class antibodies to TG2 or TG6 are more common than IgA class antibodies in patients with gluten related neurological disease, in contrast to celiac disease where IgA class antbodies are more common.

IgG class antibodies are present in only 60% of patients with coeliac disease, whereas the occurrence was 90% in patients with gluten ataxia who were positive for anti-transglutaminase. This shift from IgA to IgG might reflect the target organ involved (cerebellum rather than small bowel).

[newgfcali]

Originally Posted by jccgf

..snip..

anti-TG6 (TG6 IgA and IgG antibodies... not widely available yet)

I bought the full text of this report last week. It's absolutely fascinating.

I've been looking for a lab that tests TG6 IgA & IgG antibodies, but have only been successful in finding one in Germany. Are there any labs in the US that do this test?

In the flowchart, I don't understand what "test for IgA deposits against TG on the biopsy" means. What is that?

[jccgf]

I don't really know the answers.... I have just heard/read that anti-tTG6 blood test is being used in research only and not yet available commercially... so if you know the test is available in Germany you know more than I do!

As for the IgA deposits that can be seen in tissue samples, the best I can do is point you to another article. I don't have any medical or lab background to know the exact method. Sorry I can't be more helpful.

Neurology. 2006 Feb 14;66(3):373-7.

http://www.ncbi.nlm.nih.gov/pubmed/16476935

Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia.
Hadjivassiliou M, Mäki M, Sanders DS, Williamson CA, Grünewald RA, Woodroofe NM, Korponay-Szabó IR.
Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK. m.hadjivassiliou@sheffield.ac.uk
Abstract

OBJECTIVE: To investigate the presence of autoantibody deposition against type 2 tissue transglutaminase (TG2; a reliable marker of the whole spectrum of gluten sensitivity) in the jejunal tissue and brain of patients with gluten ataxia and in control subjects. METHODS: The authors evaluated jejunal biopsy samples from nine patients with gluten ataxia and seven patients with other causes of ataxia for the presence of TG2-related immunoglobulin deposits using double-color immunofluorescence. Autopsy brain tissue from one patient with gluten ataxia and one neurologically intact brain were also studied. RESULTS: IgA deposition on jejunal TG2 was found in the jejunal tissue of all patients with gluten ataxia and in none of the controls. The intestinal IgA deposition pattern was similar to that seen in patients with overt and latent celiac disease and in those with dermatitis herpetiformis. Widespread IgA deposition around vessels was found in the brain of the patient with gluten ataxia but not the control brain. The deposition was most pronounced in the cerebellum, pons, and medulla. CONCLUSIONS: Anti-tissue transglutaminase IgA antibodies are present in the gut and brain of patients with gluten ataxia with or without an enteropathy in a similar fashion to patients with celiac disease, latent celiac disease, and dermatitis herpetiformis but not in ataxia control subjects. This finding strengthens the contention that gluten ataxia is immune mediated and belongs to the same spectrum of gluten sensitivity as celiac disease and dermatitis herpetiformis.

PMID: 16476935

[newgfcali]

Originally Posted by jccgf

I don't really know the answers.... I have just heard/read that anti-tTG6 blood test is being used in research only and not yet available commercially... so if you know the test is available in Germany you know more than I do!

As for the IgA deposits that can be seen in tissue samples, the best I can do is point you to another article. I don't have any medical or lab background to know the exact method. Sorry I can't be more helpful.

I was wrong in saying the lab in Germany was doing testing. They're actually producing the ELISA test kits for testing TG6 antibody presence. The name of the company Zedira. If you look under "products for celiac disease diagnosis" then click ELISA kits, you'll see two new entries for TG6 kits, one for IgA and one for IgG.

I believe Dr. H's research has connected the presence of TG6 antibodies with gluten ataxia, but I don't know if the same is true for gluten neuropathy.

Regarding the IgA deposits, I'm reminded of the line from Ghostbusters: "We'd like to get a sample of your brain tissue." Um.... I think maybe I'll hold off on this particular test.

[jccgf]

I'm also not sure I've seen specific mention of anti-tTG6 in peripheral neuropathy, although I've seen other articles reference it more generally.

Gluten sensitivity:an emerging issue behind neurological impairment?
http://www.ncbi.nlm.nih.gov/pubmed/20170835

"Additionally, antibodies to TG6 have have been found in the sera of patients with neurological disorders. Preliminary data suggest that antibodies to TG6 are markers for neurological gluten sensitivity, whereas antibodies to TG3 might be markers for dermatitis herpetiformis."

Course, the reference points back to Hadjivasilliou 2008.

In Dr. H's paper, there are some generalized references of anti-tTG6 to neurological dysfunction or neurological manifestation but when I look for specific references I only see anti-tTG6 in reference to gluten ataxia.

I have seen (I'm sure you have, too) reference to anti-Purkinje cell in patients with cerebellar ataxia and anti-ganglioside antibodies in patients with peripheral neuropathy.

[newgfcali]

Originally Posted by jccgf

I have seen (I'm sure you have, too) reference to anti-Purkinje cell in patients with cerebellar ataxia and anti-ganglioside antibodies in patients with peripheral neuropathy.

Correct me if I'm wrong, but I believe the correlation between anti-ganglioside antibodies and neuropathy is primarily motor neuropathy rather than sensory. I think that's why I haven't paid close attention to that line of research -- I'm not exhibiting any motor degradation (at this time).

[darlindeb25]

Correct me if I'm wrong, but I believe the correlation between anti-ganglioside antibodies and neuropathy is primarily motor neuropathy rather than sensory.

I'm not well versed in the technical talk, but I do know I have ganglioside antibodies and sensory neuropathy, not motor neuropathy. I had never heard of ganglioside antibodies until my neuro tested me for them.

[newgfcali]

Originally Posted by darlindeb25

I not well versed in the technical talk, but I do know I have ganglioside antibodies and sensory neuropathy, not motor neuropathy. I had never heard of ganglioside antibodies until my neuro tested me for them.

Deb - you and I are so similar, double dq1, gluten sensitive, etc. I will add this to my list to check out, too. Sounds like your neuro is pretty sharp. Thanks for this piece of the puzzle.

I have my first neuro appointment scheduled and have a laundry list of questions. My biggest concern is that this is hereditary, not acquired due to gluten sensitivity like I've been thinking these past six months. If it's hereditary I'm afraid there isn't going to be anything I can do to stop it. My dad has severe PN in both legs up to his knees, both sensory and motor. He's fallen a number of times because he trips over his feet. I'm desperately searching for answers so I don't end up there when I get to be his age. He's never been to a doctor for it, so we don't know the cause.

[darlindeb25]

I have my first neuro appointment scheduled and have a laundry list of questions. My biggest concern is that this is hereditary, not acquired due to gluten sensitivity like I've been thinking these past six months. If it's hereditary I'm afraid there isn't going to be anything I can do to stop it. My dad has severe PN in both legs up to his knees, both sensory and motor. He's fallen a number of times because he trips over his feet. I'm desperately searching for answers so I don't end up there when I get to be his age. He's never been to a doctor for it, so we don't know the cause

Just a thought for you to ponder...gluten sensitivity is hereditary too. Very well could be, your dad is gluten intolerant, and that's why he has the neuropathy to begin with. Find out if you are gluten intolerant, also find out your B12 level, and Vit D. They both are very necessary for optimal health. I was deficient in both, resulting in my neuropathy, which was all caused by my gluten intolerance. Had I known about gluten to begin with, I may never have developed the neuropathy.