Serum antigliadin antibodies in cerebellar ataxias: a systematic review and meta-analysis

Correspondence to Dr Sheng-Han Kuo, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 USA ; [email protected]

Introduction

The differential diagnosis of cerebellar ataxia is broad, including hereditary and degenerative causes, and few disease-specific treatments are available. Immune-mediated cerebellar ataxias are characterised by serum or cerebrospinal fluid antibody positivity, mild or absence of the cerebellar atrophy on structural neuroimaging at the initial stage and the responsiveness to immunomodulatory therapy.^{1 2} Established immune-mediated cerebellar ataxias are relatively rare, among which gluten ataxia has been reported to be the most common. Gluten ataxia refers to cerebellar ataxia associated with gluten sensitivity, a prominent immunological response to gluten intake, for which the human body produces abnormally high titres of serum antigluten antibodies.^{3 4} Gluten sensitivity is considered a gluten-related disorder separate from coeliac disease, which is characterised by the presence of antibodies to tissue transglutaminase 2 (TTG2) and inflammatory changes in the small intestine.⁵ Patients with gluten sensitivity lack these changes; however, might have evidence of alterations in intestinal permeability.⁶ The presence of antibodies to gliadin is considered to represent a form of gluten sensitivity.⁷ Patients with cerebellar ataxia with antigluten antibodies could respond to gluten-free diet or immunoglobulin therapy,² representing a treatable form of cerebellar ataxia.

Antigluten antibodies are generated in response to gluten proteins existing in wheat, rye and barley, among which antigliadin antibody (AGA) is most studied in patients with cerebellar ataxia.⁸ AGA has been reported in 43% of otherwise idiopathic cerebellar ataxia (IDCA) cases; however, AGA is also found in up to 12% controls and in 13% hereditary ataxia (HA) cases.^{9 10} When comparing with controls, IDCA cases are thus more commonly reported to have AGA seropositivity.¹⁰ However, these results have been inconsistently replicated.^{3 11–14} Several factors such as ethnic backgrounds and different methodologies used for AGA detection have been postulated to explain the discrepancy between studies,¹² but there is no systematic review for these important questions. Therefore, we performed a meta-analysis to examine the association between AGA seropositivity and cerebellar ataxia and to investigate the factors accounting for the discrepancies between studies.

Methods

Data sources and searches

The methodology used for the systematic review and meta-analysis followed...