HLA Analysis in Autoimmune Encephalitis and Related Disorders (ICARE)

Immunogenetic Characteristics in Autoimmune Encephalitis and Related Disorders: HLA Analysis

Autoimmune encephalitis (AE) are characterized by subacute onset of memory deficits, altered mental status or psychiatric symptoms, frequently associated with seizures, inflammatory cerebrospinal fluid and in cases with prominent limbic involvement, typical magnetic resonance imaging. Several autoantibodies (Ab) may be detected in AE, although its detection is not mandatory to establish a diagnosis. These Ab mainly recognize different synaptic and cell-surface proteins in the central nervous system, and are thought to be pathogenic as they alter the normal location or function of its antigens.

The primary trigger of the immune response is unknown for most of AE. In addition to acquired susceptibility, genetic predisposition may also be important in the pathogenesis of AE. Human leukocyte antigen (HLA) is the genetic factor most frequently associated with autoimmune diseases, due to its genetic complexity and key role in the adaptive immune response. The aim of the study is to describe HLA profile in three groups of autoimmune encephalitis and related disorders: anti-LGI1, anti-CASPR2 and anti-GAD neurological diseases.

Study Overview

• Status: Unknown
• Conditions: Autoimmune Encephalitis; Imbic Encephalitis; Autoimmune Cerebellar Ataxia; Stiff-person Syndrome

• Study Type: Observational
• Enrollment (Anticipated): 160

Contacts and Locations

• Study Contact: Name: Jerome HONNORAT, PhD; Phone Number: 33 4 72 35 78 08; Email: jerome.honnorat@chu-lyon.fr
• Study Contact Backup: Name: Géraldine PICARD; Phone Number: 33 4 72 35 58 42; Email: geraldine.picard@chu-lyon.fr

Study Locations

• France
  • Lyon, France
    • Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes
    • Contact: Jerome HONNORAT, PhD; Phone Number: 4 72 35 78 08

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with autoimmune encephalitis or related disorders whose samples were sent for analysis at Centre de Référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, Lyon, for anti-neural antibody study and then stored at the biobank Neurobiotec

Description

Inclusion Criteria:

1. Presence of anti-LGI1, anti-CASPR2 or anti-GAD antibodies in serum or cerebrospinal fluid;
2. Clinical picture compatible with the detected antibody (limbic encephalitis in anti-LGI1; limbic encephalitis, neuromyotonia or Morvan's syndrome in anti-CASPR2; limbic encephalitis, cerebellar ataxia or stiff-person syndrome in anti-GAD

Exclusion Criteria:

- Absence of complete clinicobiological data.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Patients with antibodies against LGI1; This is a non-interventional study involving biological samples (DNA). Samples are already stored in biobank repositories and collected as part of "good clinical practice" in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the "Centre de Ressources Biologiques des Hospices Civils de Lyon" (CRB-HCL)/NeuroBioTec (including tissue, cells or biological fluids) and genetic analysis for research purposes (e.g. involving genes related to the disease for which the patient was followed). Additionally, patients will be informed about the present study.
Patients with antibodies against CASPR2; This is a non-interventional study involving biological samples (DNA). Samples are already stored in biobank repositories and collected as part of "good clinical practice" in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the "Centre de Ressources Biologiques des Hospices Civils de Lyon" (CRB-HCL)/NeuroBioTec (including tissue, cells or biological fluids) and genetic analysis for research purposes (e.g. involving genes related to the disease for which the patient was followed). Additionally, patients will be informed about the present study.
Patients with antibodies against GAD; This is a non-interventional study involving biological samples (DNA). Samples are already stored in biobank repositories and collected as part of "good clinical practice" in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the "Centre de Ressources Biologiques des Hospices Civils de Lyon" (CRB-HCL)/NeuroBioTec (including tissue, cells or biological fluids) and genetic analysis for research purposes (e.g. involving genes related to the disease for which the patient was followed). Additionally, patients will be informed about the present study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HLA in autoimmune encephalitis and related disorders	Description of HLA alleles and haplotypes carrier frequencies in autoimmune encephalitis and related disorders	12 Months
Clinical relevance of HLA in autoimmune encephalitis and related disorders	Description of clinical differences among patients regarding their HLA status	12 Months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Actual): September 27, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neurologic Manifestations; Endocrine System Diseases; Thyroid Diseases; Neuromuscular Diseases; Dyskinesias; Spinal Cord Diseases; Cerebellar Diseases; Thyroiditis, Autoimmune; Thyroiditis; Encephalitis; Ataxia; Cerebellar Ataxia; Hashimoto Disease; Stiff-Person Syndrome
• Other Study ID Numbers: iCARE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No