Israeli Researchers Propose Link Between Gluten and ALS

Celiac.com 04/23/2015 - It's well-known that many people with celiac disease experience neuropathy and other nerve disorders. Now, a team of Israeli researchers are cautiously proposing a link between gluten reactions and ALS.

The research team, from the Tel Aviv Medical Center, believes that the gluten sensitivity seen in people with celiac disease might have a connection with ALS, or amyotrophic lateral sclerosis. Their study linking tissue transglutaminase 6 antibodies to ALS is the first study to document a connection between ALS and antibodies to a particular enzyme. Also known as Lou Gehrig's disease, ALS is a progressive disease that attacks nerve cells and pathways in the brain and spinal cord, eventually causing paralysis.

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In the study, researcher Vivian Drory and her team found antibodies to an enzyme produced in the brain, called tissue transglutaminase 6 (TG6), in 23 out of 150 patients with ALS, but in only five of 115 healthy volunteer subjects. Furthermore, ALS patients showed higher concentrations of those antibodies.

It's well documented that people with celiac disease produce antibodies to another transglutaminase, TG2, when they eat gluten, a protein in wheat, barley and rye. Interestingly, nearly half (45%) of patients with celiac disease also produce antibodies to TG6, even when they have no neurological symptoms.

Droury's team set out to evaluate the prevalence of celiac disease-related antibodies and HLA antigen alleles, as well as TG6 antibodies, in patients with ALS and healthy individuals serving as controls to determine whether a neurologic presentation of a gluten-related disorder mimicking ALS might occur in some patients.

They conducted a case-control study in an ALS tertiary center, where they measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase 2 (TG2) and endomysium, along with IgA and IgG antibodies to deamidated gliadine peptide and TG6 and performed HLA antigen genotyping in 150 consecutive patients with ALS and 115 healthy volunteers of similar age and sex.

Study subjects did not have any known autoimmune or gastroenterologic disorder, and none was receiving any immunomodulatory medications.

The team found that ALS patients with antibodies to TG6 showed the classic picture of ALS and the typical rate of disease progression. The volunteers with antibodies to TG6 showed no signs of any disease.

All patients and control group participants were seronegative to IgA antibodies to TG2, endomysium, and deamidated gliadine peptide. Twenty-three patients (15.3%) were seropositive to TG6 IgA antibodies as opposed to only 5 controls (4.3%) (P = .004). The patients seropositive for TG6 showed a classic picture of ALS, similar to that of seronegative patients.

The team tested fifty patients and 20 controls for celiac disease-specific HLA antigen alleles; 13 of 22 TG6 IgA seropositive individuals (59.1%) tested seropositive for celiac disease-related alleles compared with 8 (28.6%) of the 28 seronegative individuals (P = .04).

Average levels of IgA antibodies to TG6 were 29.3 (30.1) in patients and 21.0 (27.4) in controls (P = .02; normal, <26). Average levels of IgA antibodies to TG2 were 1.78 (0.73) in patients and 1.58 (0.68) in controls (normal, <10). In a subset of study participants, mean levels of deamidated gliadin peptide autoantibodies were 7.46 (6.92) in patients and 6.08 (3.90) in controls (normal, <16).

None of the ALS patients or volunteers had the antibodies to TG2 that are commonly associated with celiac disease, but the ALS patients were more likely to show the genetic mutations that put them at risk for celiac disease.

Drory said her team has begun to study TG6 antibody levels in patients newly diagnosed with ALS, and they will be testing the effects of a gluten-free diet in some of those that test positive. However, theirs is just one report, and Drory expects it will be at least a couple of years before the team has any solid results. Her team is also inviting further input from other centers, and study of their data.

In the meantime, she warns ALS patients against adopting a gluten-free diet without "clear evidence of antibodies," because any imbalance of diet might prove harmful. It's also worth remembering that an association is not the same as a cause. At least one earlier study concluded that there was no association between TG6 antibodies and either neurological disease or gluten itself.

The possibility of a link between celiac disease and a degenerative nerve disease like ALS is interesting, to say the least. The findings of this team will likely invite more examination of any connection between gluten reactions and nerve disorders, so stay tuned for any follow-up news.

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