Autoimmunity in Neurologic Complications of Celiac Disease
Condition: Ataxia
MeSH terms: Celiac Disease; Ataxia
Study type: Observational

Summary: 
      This study, done in collaboration with Cornell University in New York, will explore the
      potential role of the body s immune response to gluten in ataxia. Celiac disease is an
      autoimmune disorder that is triggered by the ingestion of wheat gluten and related proteins
      in genetically susceptible individuals. Some people with celiac disease also develop ataxia,
      which is a loss of muscle coordination, leading to imbalance. The cause of the associated
      ataxia is not well understood, but it is suspected to be related to the immune response
      towards gluten in these patients. Preliminary results indicate that antibodies in people with
      celiac disease can react with brain proteins, which might have a role in the associated
      neurologic deficits. The aim of this study is to characterize the immune response in the
      ataxia that is associated with celiac disease.

      People 18 years of age and older with 1) ataxia and no celiac disease, 2) ataxia plus celiac
      disease and 3) matched healthy control subjects will be enrolled at the NIH. People with
      celiac disease only will be enrolled at Cornell University.

      All participants have a blood sample drawn for various tests of immune function as well as
      genetic tests. Healthy volunteers also have a history and physical examination if they have
      not had one done at NIH in the past year. Some patients may require additional clinical
      evaluations for clinical or diagnostic reasons.
    

Detailed description: 
      Objective: To understand the role of the immune system in the neurologic complications of
      celiac disease (CD) or gluten sensitivity (GS).

      Study population: We plan to study 15 patients with CD and ataxia, 15 patients with
      hereditary ataxia, and 30 healthy matched controls.

      Design: Four groups of patients will be enrolled into the study. The first group will consist
      of patients with CD and ataxia, the second group will consist of CD patients without
      neurological manifestations, the third group will consist of patients with hereditary
      cerebellar ataxia without CD, and the final group will consist of healthy 30 race matched
      volunteers. The second group will not be recruited at the NIH. Standardized enzyme-linked
      immunosorbent assay (ELISA) techniques will used to assess the presence of synapsin I in the
      groups of patients. Using affinity assays, cross-reactivity of antibodies to gliadin and
      synapsin 1 will be evaluated. Antibody epitope mapping will be performed on those antibodies
      that cross-react with synapsin 1 and gliadin. HLA class II genotypic and phenotypic
      frequencies will be assessed and compared with the matched volunteers as an exploratory
      measure to look for genetic risk and protective factors in this group of patients.

      Outcome measures: our outcome measures are as follows:

      A. To determine whether there is an association between antibody reactivity to synapsin I and
      neurological deficits of CD/GS.

      B. To characterize the cross-reactive antibodies in patients by determining subclass and
      affinity

      C. To map the epitope(s) of synapsin I that are targeted in patients with cross-reactive
      antibodies

      D. To explore HLA association in the subset of patients with CD and ataxia
    

Time perspective: Prospective
Keywords: Celiac Disease; Ataxia; Adults; Health Volunteer; HV