Autoimmunity in Neurologic Complications of Celiac Disease
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.
|Study Design:||Time Perspective: Prospective|
|Official Title:||The Role of Autoimmunity in Neurologic Complications of Celiac Disease|
- Antibodies to synapsin I.
- Antibody characterization and HLA association
|Study Start Date:||June 2008|
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
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, New York|
|New York, New York, United States, 10021-4872|
|Principal Investigator:||Mark Hallett, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|