Mitochondrial Disease-associated ImmunoDeficiencies (MitoID)

Determining the Relevance of Mitochondrial Disease-associated ImmunoDeficiencies - MitoID

The study aims at characterizing the immune dysfunctions in patients with mitochondrial diseases. This has prognostic and diagnostic interest as well as potential for the discovery of new therapeutic strategies to alleviate disease burden.

Study Overview

• Status: Recruiting
• Conditions: Mitochondrial Disorders
• Intervention / Treatment: Procedure: Patient cohort; Procedure: Control cohort

Detailed Description

Mitochondrial pathologies are rare genetic diseases, and affect about 1 in 4300 people. These pathologies are characterized by an energetic deficit that can affect all organs, and can manifest from birth to adulthood. The clinical expression is very heterogeneous, the symptoms can include encephalopathies, myopathies, cardiomyopathies, among others, with frequently "an illegitimate association of symptoms" that add up in a progressive way. These pathologies are related to the presence of pathogenic mutations in the genes of the nuclear genome involved in mitochondrial metabolism, or directly in the genes of the mitochondrial DNA (mtDNA).

The immune system dysfunctions associated with mitochondrial diseases remain unknown to date despite the presence of the deleterious variant in leukocytes. Recent studies by group of the investigators and others in animal models clearly show the importance of mitochondrial functions in the regulation of inflammatory and antimicrobial processes. These experimental data are particularly relevant in light of recent clinical studies indicating that patients with mitochondriopathies have a higher rate of bacterial infections compared to control individuals.

The investigators hypothesized that immunological parameters assessment in patients will reveal new dysfunctions associated with these pathologies and that some of these parameters will be a prognostic factor in these "step-like" progression of these diseases.

This study will recruit 30 patients with mitochondrial disorders followed in Bordeaux University Hospital and Toulouse University Hospital for who the mutation of mitochondrial DNA has been previously identified. Among classical disease activity information, blood samples will be collected to study immunological parameters. Translational research will be realized on patient' samples to assess immune cell subsets and innate immune cells functions.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Aurélien TRIMOUILLE, MD; Phone Number: +335 57 82 10 49; Email: aurelien.trimouille@chu-bordeaux.fr
• Study Contact Backup: Name: Johan Garaude, MD; Email: johan.garaude@inserm.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU Bordeaux
    • Contact: Aurélien TRIMOUILLE, MD
  • Toulouse, France, 31059
    • Not yet recruiting
    • Hopital Toulouse
    • Contact: Olivier PATAT, MD; Email: patat.o@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

• Patient cohort : Patient with moleculary proven mitochondrial disorder
• Control cohort : People without moleculary proven mitochondrial disorder

Description

Inclusion Criteria:

• General inclusion criteria:

  • Patient weighing more than 30kg
  • Person affiliated with or receiving a social security plan;

• Patient-specific inclusion criteria:

  • Patient with molecularly proven primary mitochondrial disease
  • Free, informed, written consent signed by parental authority holders for minor patients and the investigator prior to any examination required by the research and oral and/or written assent by the participant (depending on age).
  • Free, informed consent signed by the patient's representative for adult patients under guardianship and the investigator prior to any examination required by the research.
  • Free, informed consent signed by the patient of legal age and the investigator prior to any examination required by the research

• Specific inclusion criteria for controls:

  • Person who has been informed of the purpose of the study and person matched in age (+/- 5 years) and sex to a patient with primary mitochondrial disease at the time of sampling
  • Free, informed, and signed consent
  • Person with no known mitochondrial disease

Exclusion Criteria:

• Pregnant or breastfeeding women
• Refusal to consent to participate in research,
• Patients for whom molecular causes have not been formally identified (genetic analyses not performed, or no variant or variant of unknown significance after analysis).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
o Patient cohort; Patient with moleculary proven mitochondrial disorder	Procedure: Patient cohort; Collection of 6 blood tubes at the inclusion visit.
o Control cohort; People without moleculary proven mitochondrial disorder	Procedure: Control cohort; Collection of 6 blood tubes at the inclusion visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological parameters	Distribution of several quantitative immunological parameters at inclusion. The following parameters will be considered : Immunoglobulins in g/l (IgG subclasses, IgA, IgM)	Inclusion visit
Immunological parameters	Distribution of several quantitative immunological parameters at inclusion. The following parameters will be considered : multiplex flow cytometry panels (Th1, Th2, Th17, Tfh, T, B, monocytes) in fluorescence intensity unit	Inclusion visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological parameters	Description of the percentage of patients with abnormal immunological parameters	Inclusion visit
infectious events	Incidence of severe or recurrent infectious events retrospectively compared to the general population	Inclusion visit
Biological markers	Description of the percentage of patients with abnormal key cytokines (TNF, IL-1b, IL-6, IL-12)	Inclusion visit

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Aurélien TRIMOUILLE, MD, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: June 9, 2023
• First Submitted That Met QC Criteria: January 16, 2024
• First Posted (Actual): January 19, 2024

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: immunology; mitochondrial diseases; PBMCs; scRNA-seq; scATAC-seq
• Additional Relevant MeSH Terms: Metabolic Diseases; Mitochondrial Diseases
• Other Study ID Numbers: CHUBX 2022/36

Drug and device information, study documents

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