Neurological Dysfunction in Coeliac Disease and Non-Coeliac Gluten Sensitivity

Abstract

Objectives:Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms without enteropathy that symptomatically benefit from gluten-free diet (GFD). Little is known about its pathophysiology, propensity to neurological manifestations, and if these differ from patients with coeliac disease (CD). We investigated the clinical and immunological characteristics of patients presenting with neurological manifestations with CD and those with NCGS.Methods:We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS presenting with neurological dysfunction assessed and followed up regularly over a period of 20 years.Results:Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confirm CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological dysfunction and had circulating anti-gliadin antibodies. Out of 562 patients, 228 (41%) had evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet. Anti-tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and those without as well as those with positive TG2 compared with those with negative TG2 antibodies identified no differences within these subgroups. Serological positivity for TG6 antibodies was similar in the two groups (67 and 60%).Conclusions:The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms.

Transglutaminase 6 antibodies in gluten neuropathy

“…At the same time the prevalence of TG6 in patients with non-coeliac gluten sensitivity presenting with neurological dysfunction was similar to those presenting with neurological dysfunction who also had enteropathy 60% vs 67% [6].…”

“…Amongst patients with CD the prevalence of TG6 in those presenting with classic gastrointestinal symptoms was 38% vs 67% in those presenting with neurological symptoms [6]. At the same time the prevalence of TG6 in patients with non-coeliac gluten sensitivity presenting with neurological dysfunction was similar to those presenting with neurological dysfunction who also had enteropathy 60% vs 67% [6].…”

“…Neurological manifestations of gluten sensitivity might not only occur in the context of coeliac disease (CD) but also in non-coeliac gluten sensitivity (NCGS) [6]. Although some markers such as anti-tissue transglutaminase (TG2) and anti-endomysium antibodies are sensitive and specific in diagnosing CD, such antibodies will usually be absent in patients with NCGS [6].…”

“…TG2, TG3 and TG6 share 65% homology, they are capable of deamidating gluten peptides and antibodies against TG2, TG3 and TG6 are eliminated with strict adherence to a gluten-free diet [10]. TG6 antibodies are present in 38% of patients with newly diagnosed CD but in only 4% of normal subjects [6,10]. Moreover, the prevalence of TG6 in patients with gluten ataxia is 73% [10].…”

“…Although some markers such as anti-tissue transglutaminase (TG2) and anti-endomysium antibodies are sensitive and specific in diagnosing CD, such antibodies will usually be absent in patients with NCGS [6]. Anti-gliadin antibodies, however, are indicators of NCGS as up to 50% of such patients presenting to gastroenterologists have detectable circulating levels of anti-gliadin antibodies [7].…”