X-linked Moesin Associated Immunodeficiency (X-MAIDReg)

Etude Multicentrique Internationale rétrospective Des Patients Atteints de déficit Immunitaire associé à la moésine lié au Chromosome X (X Maid Pour X-linked Moesin Associated Immunodeficiency)

Moesin deficiency was initially described in 7 male participants aged 4 to 69 years and is characterized by lymphopenia of the 3 lineages and moderate neutropenia. Genetically, 6 out of 7 participants had the same missense mutation in the moesin gene located on the X chromosome. The 7th patient has a mutation leading to the premature introduction of a STOP codon into the protein.Clinically the 7 participants with X-linked moesin-associated immunodeficiency all presented with recurrent bacterial infections of the respiratory, gastrointestinal or urinary tracts, and some had severe varicella.Therapeutically, in the absence of a molecular diagnosis and due to his SCID-like phenotype, one patient was treated with geno-identical hematopoietic stem cell transplantation . The remaining are untreated or treated with immunoglobulin substitution and/or prophylactic antibiotics.

Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The Investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigator propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each patient according to his or her clinical picture

Study Overview

• Status: Recruiting
• Conditions: Infections; Autoimmune Diseases; Diagnosis; Immune Deficiency
• Intervention / Treatment: Genetic: genetic restrospective study

Detailed Description

Since this study, the moesin gene has been integrated into DNA chips used for the molecular diagnosis of immune deficiencies in several countries. Physicians in Canada, the United States, Japan, South Africa and Europe have contacted us with a total of 16 known participants to date. Because of their very low severe, uncontrolled CMV infection and the absence of treatment recommendations, two 2 American participants were treated with allogeneic transplantation with severe post-transplant complications (1), and one of the participants died as a result of the transplant. Management of XMAID participants therefore varies widely from country to country, depending on age at diagnosis and clinical picture. It ranges from no treatment treatment (associated with recurrent infections and skin manifestations), IgIv substitution and/or antibiotic prophylaxis antibiotic prophylaxis, with low toxicity and apparent efficacy, and allogeneic transplantation, with all the risks risks involved (graft-related toxicity, graft versus host, disease, rejection, risk of infection). The investigators therefore feel it is important to review the diagnosis, clinical presentation and management of X-MAID participants. The study the investigators propose will enable to understand the presentation of X-MAID participants, establish guidelines and provide the best treatment for each participant according to his or her clinical picture

• Study Type: Observational
• Enrollment (Estimated): 16

Contacts and Locations

• Study Contact: Name: Isabelle ANDRE, Doctor; Phone Number: 01 42 75 43 37; Email: isabelle.andre@inserm.fr

Study Locations

• Australia
  • Brisbane, Australia, 4001
    • Not yet recruiting
    • Genomic Research Centre, School of Biomedical Sciences Institute of Health and Biomedical Innovation
    • Contact: Lyn Griffith, Pr
• Belgium
  • Bruxelles, Belgium, 1020
    • Not yet recruiting
    • Hôpital Universitaire de la Reine Fabiola
    • Contact: Catherine Heijmans, Doctor
• France
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker
    • Contact: Benedicte NEVEN
  • Rennes, France, 35000
    • Recruiting
    • CHU Rennes, CNRS UMR 629
    • Contact: Virginie Gandemer, Doctor
  • Saint-Étienne, France, 42270
    • Not yet recruiting
    • CHU St Etienne Hôpital Nord
    • Contact: Jean-Louis STEPHAN, Doctor
• Japan
  • Bunkyō-Ku, Japan, 1138510
    • Not yet recruiting
    • Tokyo Medical and Dental University (TMDU)
    • Contact: Kohsuke Imai, Pr
• Netherlands
  • Rotterdam, Netherlands
    • Not yet recruiting
    • Departments of Internal Medicine and Immunology
    • Contact: Virgil Dalm
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Not yet recruiting
      • National Institutes of Health
      • Contact: Luigi Notarangelo, Doctor
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19050
      • Not yet recruiting
      • Perelman School of medecine
      • Contact: Jennifer Heimall, Pr
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Not yet recruiting
      • Brown University
      • Contact: Anthony Hayward

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Given the small number of participants and the purpose of the study, the group may include deceased patients (at least 1 of the 16 participants). The sample size is 16 patients already identified, and possibly other patients who may be identified once the existence of the the existence of the international registry. Final enrolment will correspond to all X-MAID patients diagnosed worldwide who agree to take part in the study.

Description

Inclusion Criteria:

• Male patient with a mutation in the MOESIN gene (MSN)
• No objection to the collection of personal health data

Exclusion Criteria:

-

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main objective	The main objective is to study the clinical results of the different therapeutic options applied to X-MAID patients, and to investigate whether there is a correlation between treatment responses and mutation position	through study completion, and average 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary objectives1	Circumstances of genetic diagnosis: at what age are these patients diagnosed, and by what means? (role of prenatal screening).	through study completion, and average 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
secondary objectives 2	What is the state of their immune system and, depending on this state, the CID or SCID classification of the disease.	through study completion, and average 3 years
secondary objective 3	What are the clinical manifestations of the disease (cutaneous, infectious, autoimmune)?	All the patients are male. As a result of their immune deficiency, patients suffer from recurrent bacterial infections of the respiratory, digestive and urinary tracts, as well as, in some cases, skin manifestations such as eczema, alopecia and molluscum
secondary objectives 4	What impact does the disease have on their development?	Among patients diagnosed in the first years of life, none showed developmental defects.
secondary objective 5	What are the treatments and their consequences?	Treatments range from no prophylaxis at all to antibiotic prophylaxis, with or without immunoglobulin therapy, granulocyte-colony-stimulating factor therapy or hematopoietic stem cell allograft.

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Isabelle ANDRE, doctor, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2021
• Primary Completion (Estimated): August 12, 2026
• Study Completion (Estimated): January 12, 2027

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Estimated): February 26, 2024

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes; Autoimmune Diseases
• Other Study ID Numbers: C19-35

Drug and device information, study documents

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