Autoimmunity in Neurologic Complications of Celiac Disease

• INCLUSION CRITERIA:

We plan to evaluate serum and blood from patients with gluten sensitivity (including both biopsy-proven CD, and biopsy-negative cases with high anti-gliadin antibody titer) accompanied by cerebellar ataxia. Serum samples will be acquired prior to initiation of a gluten-free diet. Therefore, several inclusion criteria exist based on the study group:

INCLUSION CRITERIA FOR PATIENTS WITH CD PLUS CEREBELLAR ATAXIA:

• The patient meets criteria for CD based on the modified ESPGAN criteria
• The patient has ataxia with or without neuropathy based on clinical evaluation
• The patient is free from other neurological and psychiatric deficits
• All other known causes for ataxia have been ruled out through routine clinical evaluations
• The patient is at least 18 years old and is willing to participate in the protocol
• The patient is not taking medications that are commonly known to have immune modulating effects.
• The patient is not on a gluten free diet

INCLUSION CRITERIA FOR PATIENTS WITH HEREDITARY CEREBELLAR ATAXIA WITHOUT CD:

• The patient tested negative for serologic markers of CD (i.e. antigliadin, antireticulin, and antiendomysial antibody testing as performed under protocol 93-N-0202)
• The patient has ataxia on routine clinical examination and no other neurological or psychiatric problems
• The patient has a known autosomal dominant ataxia (i.e., SCA, DRPLA, Friedreich s ataxia, and etc).

INCLUSION CRITERIA FOR MATCHED-CONTROLS:

• They should not have CD and or ataxia based on clinical evaluation and history
• Serologic testing for antigliadin, antireticulin, and antiendomysial antibodies should reveal negative results
• They should be race and age-matched with patients with CD and the ataxia group.
• They should have no neurological or psychiatric conditions based on clinical evaluation and history
• They should not have any rheumatological or autoimmune conditions in them or in their first degree relatives.
• They should be at least 18 years of age and be able to provide consent for participation
• They should not be on any immune modulating medications.

Final diagnosis of CD will strictly follow the modified criteria of the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) and recommendations of the recently held National Institutes of Health Consensus Development Conference on Celiac Disease. Assessment and diagnosis of cerebellar ataxia will be made by magnetic resonance imaging of the brain, clinical examination and genetic testing for spinocerebellar ataxias and Friedreich s ataxia. Additional routine testing will be done if necessary to exclude other causes.

Healthy and disease control groups will be evaluated for CD and for neurological deficits. Only symptom-free, antibody-negative individuals will be recruited into these control groups. Exclusion of neurological deficits and psychiatric illness in healthy and disease control subjects will be by history and neurological examination.

EXCLUSION CRITERIA:

For all groups, if other neurological and psychiatric diagnoses are present, the individual will not qualify to participate in this study.

EXCLUSION CRITERIA FOR ALL GROUPS:

• Subject is already on a gluten-restricted diet.
• Is taking known immune modulating therapy
• Have other neurological condition (except for neuropathy) or psychiatric condition
• Not willing to have blood drawn
• Is known to have immune dysfunction
• Being pregnant leads to numerous physiological changes. It is unclear if antibody characteristics are influenced by these changes.