ALS and gluten sensitivity
ALS (amyotrophic lateral sclerosis) is a devastating, lethal autoimmune disease characterized by progressive inflammatory degeneration of motor neurons in the brain cortex, brainstem and ventral (front half) of the spinal cord. Non-celiac gluten sensitivity often entails a neurological target for autoimmune attack in the absence of abdominal symptoms. In a study just published in JAMA Neurology, investigators report an association between some cases of ALS and gluten sensitivity. They state:
"Celiac disease is an autoimmune disorder triggered by gluten in genetically predisposed individuals. Gluten sensitivity can cause neurologic manifestations, such as ataxia or neuropathy, with or without gastrointestinal symptoms. Many patients with gluten ataxia produce antibodies toward the newly identified neuronal transglutaminase 6 (TG6). Two case reports described patients initially diagnosed with amyotrophic lateral sclerosis (ALS) and ultimately with celiac disease who improved with a strict gluten-free diet."
To determine whether a gluten-related disorder mimicking ALS might occur in some patients they set out to look for celiac disease–related antibodies and HLA antigen alleles along with TG6 antibodies in patients with ALS compared to healthy individuals. They measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase 2 (TG2) and endomysium, IgA and IgG antibodies to deamidated gliadine peptide, and TG6; and performed HLA antigen genotyping in 150 patients with ALS and 115 healthy volunteers. A striking picture emerged:
"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%). The patients seropositive for TG6 showed a classic picture of ALS, similar to that of seronegative patients."
Clinical note
- Seronegativity to IgA antibodies to transglutaminase-2 (TG2) and endomysium
means that these ALS syndrome cases represent a non-celiac neurological gluten sensitivity. - Transglutaminase-6 (TG6) antibodies are included in the Wheat/Gluten Proteome Reactivity & Autoimmunity panel (Array 3) from Cyrex Laboratories.
Practitioners should bear in mind the authors' conclusion:
"The data from this study indicate that, in certain cases, an ALS syndrome might be associated with autoimmunity and gluten sensitivity. Although the data are preliminary and need replication, gluten sensitivity is potentially treatable; therefore, this diagnostic challenge should not be overlooked."